Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular funct...Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular functions such as migration, survival, proliferation, and differentiation. Oligodendrocytes are the myelin-forming cells in the central nervous system and play critical roles in the conduction of action potentials, supply of metabolic components for axons, and other functions. Emerging evidence suggests that both oligodendrocytes and oligodendrocyte precursor cells are vulnerable to cytokines released under pathological conditions. This review mainly summarizes the effects of cytokines on oligodendrocyte lineage cells in central nervous system diseases. A comprehensive understanding of the effects of cytokines on oligodendrocyte lineage cells contributes to our understanding of central nervous system diseases and offers insights into treatment strategies.展开更多
Human adult olfactory epithelium contains neural progenitors (hONPs) which replace damaged cellular components throughout life. Methods to isolate and expand the hONPs which form neurospheres in vitro have been develo...Human adult olfactory epithelium contains neural progenitors (hONPs) which replace damaged cellular components throughout life. Methods to isolate and expand the hONPs which form neurospheres in vitro have been developed in our laboratory. In response to morphogens, the hONPs differentiate along several neural lineages. This study optimized conditions for the differentiation of hONPs towards dopaminergic neurons. The hONPs were treated with Sonic hedgehog (Shh), in the presence or absence of retinoic acid (RA) and/or forskolin (FN). Transcription factors (nurr1, pitx3 and lmx1a) that promote embryonic mouse or chicken dopaminergic development were employed to determine if they would modulate lineage restriction of these adult human progenitors. Four expression vectors (pIRES-pitx3-nurr1, pLN-CX2-pitx3, pLNCX2-nurr1 and pLNCX2-lmx1a) were transfected into the hONPs, respectively. Transcription factor expression and the rate-limiting enzyme in dopamine synthesis tyrosine hydroxylase (TH) were detected in the transfected cells after 4 month-selection with G418, indicating transfected hONPs were stably restricted towards a dopaminergic lineage. Furthermore, a dopamine enzyme immunoassay (EIA) was employed to detect the synthesis and release of dopamine. The most efficient transfection paradigm was determined. Several neurotrophic factors were detected in the pre-transfected hONPs which have potential roles in the maintenance, survival and proliferation of dopaminergic neurons. Therefore the effect of transfection on the neurotrophin synthesis was examined. Transfection did not alter synthesis. The use of olfactory progenitors as a cell-based therapy for Parkinson’s disease (PD) would allow harvest without invasive surgery, provide an autologous cell population, eliminate need for immunosuppression and avoid the ethical concerns associated with embryonic tissues. This study suggests that specific transcription factors and treatment with morphogens can restrict human adult olfactory-derived progenitors to a dopaminergic neuronal lineage. Future studies will evaluate the utility of these unique cells in cell-replacement paradigms for the treatment of PD like animal models.展开更多
Glial cells in the central nervous system(CNS)are composed of oligodendrocytes,astrocytes and microglia.They contribute more than half of the total cells of the CNS,and are essential for neural development and functio...Glial cells in the central nervous system(CNS)are composed of oligodendrocytes,astrocytes and microglia.They contribute more than half of the total cells of the CNS,and are essential for neural development and functioning.Studies on the fate specification,differentiation,and functional diversification of glial cells mainly rely on the proper use of cell-or stage-specific molecular markers.However,as cellular markers often exhibit different specificity and sensitivity,careful consideration must be given prior to their application to avoid possible confusion.Here,we provide an updated overview of a list of well-established immunological markers for the labeling of central glia,and discuss the cell-type specificity and stage dependency of their expression.展开更多
To date,more than 580 million people worldwide have been diagnosed with infection by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).COVID-19(coronavirus disease 2019)not only affects lung function but als...To date,more than 580 million people worldwide have been diagnosed with infection by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).COVID-19(coronavirus disease 2019)not only affects lung function but also unexpectedly causes brain dysfunction as about a quarter of the survivors of this pandemic to have persistent cognitive impairment.While this sequela is more common in severely ill patients with COVID,those with mild symptoms also frequently experience cognitive impairment[1],and the pathogenic mechanism has not yet been elucidated.展开更多
For over a century,the structure and evolution of the nervous system have been at the center of debate among biologists.In the 19th century,Camillo Golgi first proposed that the nervous system is a syncytial continuum...For over a century,the structure and evolution of the nervous system have been at the center of debate among biologists.In the 19th century,Camillo Golgi first proposed that the nervous system is a syncytial continuum,with neurons being directly connected with shared cell membranes and cytoplasm[1].This concept is known as the reticular theory(also referred to as the syncytial theory).However,this view was later challenged by Santiago Ramon y Cajal,who put forward the neuronal doctrine[2].展开更多
Axonal myelination is an essential process for normal functioning of the vertebrate central nervous system. Proper formation of myelin sheaths around axons depends on the timely differentiation of oligodendrocytes. Th...Axonal myelination is an essential process for normal functioning of the vertebrate central nervous system. Proper formation of myelin sheaths around axons depends on the timely differentiation of oligodendrocytes. This differentiation occurs on a predictable schedule both in culture and during development. However, the timing mechanisms for oligodendrocyte differentiation during normal development have not been fully uncovered. Recent studies have identified a large number of regulatory factors, including cell-intrinsic factors and extracellular signals, that could control the timing of oligodendrocyte differentiation. Here we provide a mechanistic and critical review of the timing control of oligodendrocyte differentiation.展开更多
Development of the secondary palate displays molecular heterogeneity along the anterior-posterior axis;however, the underlying molecular mechanism remains largely unknown. MSX1 is an anteriorly expressed transcription...Development of the secondary palate displays molecular heterogeneity along the anterior-posterior axis;however, the underlying molecular mechanism remains largely unknown. MSX1 is an anteriorly expressed transcription repressor required for palate development. Here, we investigate the role of Msx1 in regional patterning of the secondary palate. The Wnt1-Cre-mediated expression of Msx1(Rosa Msx1^(Wnt1-Cre))throughout the palatal mesenchyme leads to cleft palate in mice, associated with aberrant cell proliferation and cell death. Osteogenic patterning of the hard palate in Rosa Msx1^(Wnt1-Cre)mice is severely impaired, as revealed by a marked reduction in palatine bone formation and decreased expression of the osteogenic regulator Sp7. Overexpression and knockout of Msx1 in mice show that the transcription repressor promotes the expression of the anterior palate-specific Alx1 but represses the expression of the medialposterior palate genes Barx1, Meox2, and Tbx22. Furthermore, Tbx22 constitutes a direct Msx1 target gene in the secondary palate, suggesting that Msx1 can directly repress the expression of medial-posterior specific genes. Finally, we determine that Sp7 is downstream of Tbx22 in palatal mesenchymal cells,suggesting that a Msx1/Tbx22/Sp7 axis participates in the regulation of palate development. Our findings unveil a novel role for Msx1 in regulating the anterior-posterior growth and patterning of the secondary palate.展开更多
Oligodendrocytes(OLs) are myelinating glial cells that form myelin sheaths around axons to ensure rapid and focal conduction of action potentials. Here, we found that an axonal outgrowth regulatory molecule, AATYK(apo...Oligodendrocytes(OLs) are myelinating glial cells that form myelin sheaths around axons to ensure rapid and focal conduction of action potentials. Here, we found that an axonal outgrowth regulatory molecule, AATYK(apoptosis-associated tyrosine kinase), was up-regulated with OL differentiation and remyelination. We therefore studied its role in OL differentiation. The results showed that AATYK knockdown inhibited OL differentiation and the expression of myelin genes in vitro. Moreover, AATYKdeficiency maintained the proliferation status of OLs but did not affect their survival. Thus, AATYK is essential for the differentiation of OLs.展开更多
In the developing spinal cord,the majority of oligodendrocyte progenitor cells(OPCs)are induced in the ventral neuroepithelium under the control of the Sonic Hedgehog(Shh)signaling pathway,whereas a small subset of OP...In the developing spinal cord,the majority of oligodendrocyte progenitor cells(OPCs)are induced in the ventral neuroepithelium under the control of the Sonic Hedgehog(Shh)signaling pathway,whereas a small subset of OPCs are generated from the dorsal neuroepithelial cells independent of the Shh pathway.Although dors allyderived OPCs(dOPCs)have been shown to participate in local axonal myelination in the dorsolateral regions during development,it is not known whether they are capable of migrating into the ventral region and myelinating ventral axons.In this study,we confirmed and extended the previous study on the developmental potential of dOPCs in the absence of ventrally-derived OPCs(vOPCs).In NestinSmo conditional knockout(cKO)mice,when ventral oligodendrogenesis was blocked,dOPCs were found to undergo rapid amplification,spread to ventral spinal tissue,and eventually differentiated into myelinating OLs in the ventral white matter with a temporal delay,providing genetic evidence that dOPCs are capable of myelinating ventral axons in the mouse spinal cord.展开更多
The myelin regulatory factor gene(MYRF)encodes a protein evolutionarily conserved from invertebrates to vertebrates,representing a novel type of membrane-bound transcriptional factor(MBTF).In vertebrates,MYRF protein ...The myelin regulatory factor gene(MYRF)encodes a protein evolutionarily conserved from invertebrates to vertebrates,representing a novel type of membrane-bound transcriptional factor(MBTF).In vertebrates,MYRF protein is required for myelin development and maintenance[1,2].展开更多
During the development of the central nervous system(CNS),neuroepithelial cells in the ventricular zone are multipotent stem cells that can generate neurons and macroglia(astrocytes or oligodendrocytes).It is generall...During the development of the central nervous system(CNS),neuroepithelial cells in the ventricular zone are multipotent stem cells that can generate neurons and macroglia(astrocytes or oligodendrocytes).It is generally thought that these progenitor cells sequentially produce neurons followed by glia.展开更多
Oligodendrocytes(OLs) are glial cells that form myelin sheaths around axons in the central nervous system(CNS).Loss of the myelin sheath in demyelinating and neurodegenerative diseases can lead to severe impairment of...Oligodendrocytes(OLs) are glial cells that form myelin sheaths around axons in the central nervous system(CNS).Loss of the myelin sheath in demyelinating and neurodegenerative diseases can lead to severe impairment of movement.Understanding the extracellular signals and intracellular factors that regulate OL differentiation and myelination during development can help to develop novel strategies for enhancing myelin repair in neurological disorders.Here,we report that TAPP1 was selectively expressed in differentiating OL precursor cells(OPCs).TAPP1 knockdown promoted OL differentiation and myelin gene expression in culture.Conversely,over-expression of TAPP1 in immature OPCs suppressed their differentiation.Moreover,TAPP1 inhibition in OPCs altered the expression of Erk1/2 but not AKT.Taken together,our results identify TAPP1 as an important negative regulator of OPC differentiation through the Mek/Erk signaling pathway.展开更多
Dear Editor,Although various components of the Wnt/β-catenin pathway have been investigated,there are conflicting reports on the roles of Wnt/β-catenin signaling in oligodendrogenesis and differentiation.For instanc...Dear Editor,Although various components of the Wnt/β-catenin pathway have been investigated,there are conflicting reports on the roles of Wnt/β-catenin signaling in oligodendrogenesis and differentiation.For instance,theΔExon3 mutation ofβ-catenin[1-4],which stabilizesβ-catenin by deletion of the phosphorylation site for the destruction complex,signifi cantly inhibits the differentiation of oligodendrocytes,展开更多
Dear Editor,Myelin,the lipid-rich insulation that supports the integrity of axons,enables rapid conduction of nerve impulses and information flow to distant brain areas[1].Oligodendrocytes(OLs)are glial cells that mye...Dear Editor,Myelin,the lipid-rich insulation that supports the integrity of axons,enables rapid conduction of nerve impulses and information flow to distant brain areas[1].Oligodendrocytes(OLs)are glial cells that myelinate axons with specialized lipid membrane extensions[2].OL progenitor cells(OPCs)arise from neural stem cells[3],and undergo proliferation before terminal differentiation and eventual myelination.Impairment at any stage of OL development can affect myelin formation.展开更多
Myelin is an evolutionarily novel and important structure for the proper functioning of the vertebrate nervous system.In the central nervous system (CNS), the myelin sheath is elaborated by
Glioma is the most common type of tumor in the central nervous system, accounting for around 80% of all malignant brain tumors. Previous studies showed a significant association between nuclear morphology and the mali...Glioma is the most common type of tumor in the central nervous system, accounting for around 80% of all malignant brain tumors. Previous studies showed a significant association between nuclear morphology and the malignant progress of gliomas. By virtue of integrated proteomics and genomics analyses as well as experimental validations, we identify three nuclear lamin genes(LMNA, LMNB1, and LMNB2) that are significantly upregulated in glioma tissues compared with normal brain tissues. We show that elevated expressions of LMNB1, LMNB2, and LMNA in glioma cells are highly associated with the rapid progression of the disease and the knockdown of LMNB1, LMNB2, and LMNA dramatically suppresses glioma progression in both in vitro and in vivo mouse models. Moreover, the repression of glioma cell growth by lamin knockdown is mediated by the p Rb-mediated G1-S inhibition. On the contrary, overexpression of lamins in normal human astrocytes dramatically induced nuclear morphological aberrations and accelerated cell growth. Together, our multi-omics-based analysis has revealed a previously unrecognized role of lamin genes in gliomagenesis, providing a strong support for the key link between aberrant tumor nuclear shape and the survival of glioma patients. Based on these findings, lamins are proposed to be potential oncogene targets for therapeutic treatments of brain tumors.展开更多
Noxious mechanical information is transmitted through molecularly distinct nociceptors,with pinprickevoked sharp sensitivity via A-fiber nociceptors marked by developmental expression of the neuropeptide Y receptor 2(...Noxious mechanical information is transmitted through molecularly distinct nociceptors,with pinprickevoked sharp sensitivity via A-fiber nociceptors marked by developmental expression of the neuropeptide Y receptor 2(Npy2 r)and von Frey filament-evoked punctate pressure information via unmyelinated C fiber nociceptors marked by MrgprD.However,the molecular programs controlling their development are only beginning to be understood.Here we demonstrate that Npy2 r-expressing sensory neurons are in fact divided into two groups,based on transient or persistent Npy2 r expression.Npy2 r-transient neurons are myelinated,likely including A-fiber nociceptors,whereas Npy2 r-persistent ones belong to unmyelinated pruriceptors that co-express Nppb.We then showed that the transcription factors NFIA and Runx1 are necessary for the development of Npy2 r-transient A-fiber nociceptors and MrgprD^+C-fiber nociceptors,respectively.Behaviorally,mice with conditional knockout of Nfia,but not Runx1 showed a marked attenuation of pinprick-evoked nocifensive responses.Our studies therefore identify a transcription factor controlling the development of myelinated nociceptors.展开更多
基金supported by the Natural Science Foundation of Zhejiang Province,No.LQ23C090003 (to CZ)the Major Project on Brain Science and Analog Brain Research of Ministry of Science and Technology of China,No.2022ZD0204701 (to MQ)the National Natural Science Foundation of China,No.32170969 (to MQ)。
文摘Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular functions such as migration, survival, proliferation, and differentiation. Oligodendrocytes are the myelin-forming cells in the central nervous system and play critical roles in the conduction of action potentials, supply of metabolic components for axons, and other functions. Emerging evidence suggests that both oligodendrocytes and oligodendrocyte precursor cells are vulnerable to cytokines released under pathological conditions. This review mainly summarizes the effects of cytokines on oligodendrocyte lineage cells in central nervous system diseases. A comprehensive understanding of the effects of cytokines on oligodendrocyte lineage cells contributes to our understanding of central nervous system diseases and offers insights into treatment strategies.
文摘Human adult olfactory epithelium contains neural progenitors (hONPs) which replace damaged cellular components throughout life. Methods to isolate and expand the hONPs which form neurospheres in vitro have been developed in our laboratory. In response to morphogens, the hONPs differentiate along several neural lineages. This study optimized conditions for the differentiation of hONPs towards dopaminergic neurons. The hONPs were treated with Sonic hedgehog (Shh), in the presence or absence of retinoic acid (RA) and/or forskolin (FN). Transcription factors (nurr1, pitx3 and lmx1a) that promote embryonic mouse or chicken dopaminergic development were employed to determine if they would modulate lineage restriction of these adult human progenitors. Four expression vectors (pIRES-pitx3-nurr1, pLN-CX2-pitx3, pLNCX2-nurr1 and pLNCX2-lmx1a) were transfected into the hONPs, respectively. Transcription factor expression and the rate-limiting enzyme in dopamine synthesis tyrosine hydroxylase (TH) were detected in the transfected cells after 4 month-selection with G418, indicating transfected hONPs were stably restricted towards a dopaminergic lineage. Furthermore, a dopamine enzyme immunoassay (EIA) was employed to detect the synthesis and release of dopamine. The most efficient transfection paradigm was determined. Several neurotrophic factors were detected in the pre-transfected hONPs which have potential roles in the maintenance, survival and proliferation of dopaminergic neurons. Therefore the effect of transfection on the neurotrophin synthesis was examined. Transfection did not alter synthesis. The use of olfactory progenitors as a cell-based therapy for Parkinson’s disease (PD) would allow harvest without invasive surgery, provide an autologous cell population, eliminate need for immunosuppression and avoid the ethical concerns associated with embryonic tissues. This study suggests that specific transcription factors and treatment with morphogens can restrict human adult olfactory-derived progenitors to a dopaminergic neuronal lineage. Future studies will evaluate the utility of these unique cells in cell-replacement paradigms for the treatment of PD like animal models.
基金supported by the National Natural Science Foundation of China(31900703 and 32170969)a Ministry of Science and Technology China Brain Initiative Grant(2022ZD0204701).
文摘Glial cells in the central nervous system(CNS)are composed of oligodendrocytes,astrocytes and microglia.They contribute more than half of the total cells of the CNS,and are essential for neural development and functioning.Studies on the fate specification,differentiation,and functional diversification of glial cells mainly rely on the proper use of cell-or stage-specific molecular markers.However,as cellular markers often exhibit different specificity and sensitivity,careful consideration must be given prior to their application to avoid possible confusion.Here,we provide an updated overview of a list of well-established immunological markers for the labeling of central glia,and discuss the cell-type specificity and stage dependency of their expression.
基金supported by the National Natural Science Foundation of China(32170969)the Zhejiang Provincial Natural Science Foundation of China(LY22H090002).
文摘To date,more than 580 million people worldwide have been diagnosed with infection by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).COVID-19(coronavirus disease 2019)not only affects lung function but also unexpectedly causes brain dysfunction as about a quarter of the survivors of this pandemic to have persistent cognitive impairment.While this sequela is more common in severely ill patients with COVID,those with mild symptoms also frequently experience cognitive impairment[1],and the pathogenic mechanism has not yet been elucidated.
基金supported by the Ministry of Science and Technology China Brain Initiative Grant(2022ZD0204701)the Scientific Research Fund of Zhejiang Provincial Education Department(Y202147674)。
文摘For over a century,the structure and evolution of the nervous system have been at the center of debate among biologists.In the 19th century,Camillo Golgi first proposed that the nervous system is a syncytial continuum,with neurons being directly connected with shared cell membranes and cytoplasm[1].This concept is known as the reticular theory(also referred to as the syncytial theory).However,this view was later challenged by Santiago Ramon y Cajal,who put forward the neuronal doctrine[2].
基金supported by grants from the National Basic Research Development Program of China(2013CB5313002012CB910402)+4 种基金the National Natural Science Foundation of China(31071879, 31000488)Major Science and Technology Projects of Zhejiang Province, China(2011C13030)the Natural Science Foundation of Zhejiang Province, China(Z2100730)the NiH(R01-NS37717)National Multiple Sclerosis Society (RG3276)
文摘Axonal myelination is an essential process for normal functioning of the vertebrate central nervous system. Proper formation of myelin sheaths around axons depends on the timely differentiation of oligodendrocytes. This differentiation occurs on a predictable schedule both in culture and during development. However, the timing mechanisms for oligodendrocyte differentiation during normal development have not been fully uncovered. Recent studies have identified a large number of regulatory factors, including cell-intrinsic factors and extracellular signals, that could control the timing of oligodendrocyte differentiation. Here we provide a mechanistic and critical review of the timing control of oligodendrocyte differentiation.
基金supported by grants from the National Natural Scientific Foundation of China (81771028 and 317771593)Medical Health Science and Technology Project of Zhejiang (2021KY891)Medical Health Science and Technology Major Project of Hangzhou (Z20200046)。
文摘Development of the secondary palate displays molecular heterogeneity along the anterior-posterior axis;however, the underlying molecular mechanism remains largely unknown. MSX1 is an anteriorly expressed transcription repressor required for palate development. Here, we investigate the role of Msx1 in regional patterning of the secondary palate. The Wnt1-Cre-mediated expression of Msx1(Rosa Msx1^(Wnt1-Cre))throughout the palatal mesenchyme leads to cleft palate in mice, associated with aberrant cell proliferation and cell death. Osteogenic patterning of the hard palate in Rosa Msx1^(Wnt1-Cre)mice is severely impaired, as revealed by a marked reduction in palatine bone formation and decreased expression of the osteogenic regulator Sp7. Overexpression and knockout of Msx1 in mice show that the transcription repressor promotes the expression of the anterior palate-specific Alx1 but represses the expression of the medialposterior palate genes Barx1, Meox2, and Tbx22. Furthermore, Tbx22 constitutes a direct Msx1 target gene in the secondary palate, suggesting that Msx1 can directly repress the expression of medial-posterior specific genes. Finally, we determine that Sp7 is downstream of Tbx22 in palatal mesenchymal cells,suggesting that a Msx1/Tbx22/Sp7 axis participates in the regulation of palate development. Our findings unveil a novel role for Msx1 in regulating the anterior-posterior growth and patterning of the secondary palate.
基金supported by the National Natural Sciences Foundation of China (31471955)the Natural Science Foundation of Zhejiang Province, China (LY17C090006+1 种基金 Q16C090017 LY18H090014)
文摘Oligodendrocytes(OLs) are myelinating glial cells that form myelin sheaths around axons to ensure rapid and focal conduction of action potentials. Here, we found that an axonal outgrowth regulatory molecule, AATYK(apoptosis-associated tyrosine kinase), was up-regulated with OL differentiation and remyelination. We therefore studied its role in OL differentiation. The results showed that AATYK knockdown inhibited OL differentiation and the expression of myelin genes in vitro. Moreover, AATYKdeficiency maintained the proliferation status of OLs but did not affect their survival. Thus, AATYK is essential for the differentiation of OLs.
基金the Natural Science Foundation of Zhejiang Province,China(LQ17C040001,LQ20C090004,and LQ18C090005)the National Natural Science Foundation of China(31871480,81771028,and 31771621)。
文摘In the developing spinal cord,the majority of oligodendrocyte progenitor cells(OPCs)are induced in the ventral neuroepithelium under the control of the Sonic Hedgehog(Shh)signaling pathway,whereas a small subset of OPCs are generated from the dorsal neuroepithelial cells independent of the Shh pathway.Although dors allyderived OPCs(dOPCs)have been shown to participate in local axonal myelination in the dorsolateral regions during development,it is not known whether they are capable of migrating into the ventral region and myelinating ventral axons.In this study,we confirmed and extended the previous study on the developmental potential of dOPCs in the absence of ventrally-derived OPCs(vOPCs).In NestinSmo conditional knockout(cKO)mice,when ventral oligodendrogenesis was blocked,dOPCs were found to undergo rapid amplification,spread to ventral spinal tissue,and eventually differentiated into myelinating OLs in the ventral white matter with a temporal delay,providing genetic evidence that dOPCs are capable of myelinating ventral axons in the mouse spinal cord.
基金This insight article was supported by the Natural Science Foundation of Zhejiang Province(LQ19C090001)the National Natural Science Foundation of China(31900703 and 31771621).
文摘The myelin regulatory factor gene(MYRF)encodes a protein evolutionarily conserved from invertebrates to vertebrates,representing a novel type of membrane-bound transcriptional factor(MBTF).In vertebrates,MYRF protein is required for myelin development and maintenance[1,2].
基金the Natural Science Foundation of Zhejiang Province(LQ19C090001)the National Natural Science Foundation of China(31900703 and 31771621).
文摘During the development of the central nervous system(CNS),neuroepithelial cells in the ventricular zone are multipotent stem cells that can generate neurons and macroglia(astrocytes or oligodendrocytes).It is generally thought that these progenitor cells sequentially produce neurons followed by glia.
基金supported by the National Natural Sciences Foundation of China (31471955 and 31372150)the National Basic Research Development Program (973 Program) of China (2013CB531300)
文摘Oligodendrocytes(OLs) are glial cells that form myelin sheaths around axons in the central nervous system(CNS).Loss of the myelin sheath in demyelinating and neurodegenerative diseases can lead to severe impairment of movement.Understanding the extracellular signals and intracellular factors that regulate OL differentiation and myelination during development can help to develop novel strategies for enhancing myelin repair in neurological disorders.Here,we report that TAPP1 was selectively expressed in differentiating OL precursor cells(OPCs).TAPP1 knockdown promoted OL differentiation and myelin gene expression in culture.Conversely,over-expression of TAPP1 in immature OPCs suppressed their differentiation.Moreover,TAPP1 inhibition in OPCs altered the expression of Erk1/2 but not AKT.Taken together,our results identify TAPP1 as an important negative regulator of OPC differentiation through the Mek/Erk signaling pathway.
基金supported by the National Basic Research Development Program of China (2013CB531303, 2012CB910402)the National Natural Science Foundation of China (31101642, 31372150)+1 种基金the Science and Technology Key Project of Zhejiang Province, China (2011C13030)the National Institutes of Health, USA (R01-NS37717)
文摘Dear Editor,Although various components of the Wnt/β-catenin pathway have been investigated,there are conflicting reports on the roles of Wnt/β-catenin signaling in oligodendrogenesis and differentiation.For instance,theΔExon3 mutation ofβ-catenin[1-4],which stabilizesβ-catenin by deletion of the phosphorylation site for the destruction complex,signifi cantly inhibits the differentiation of oligodendrocytes,
基金supported by the Natural Science Foundation of Zhejiang Province,China(LY17C090006,LQ16C090004,and LY18H090014)。
文摘Dear Editor,Myelin,the lipid-rich insulation that supports the integrity of axons,enables rapid conduction of nerve impulses and information flow to distant brain areas[1].Oligodendrocytes(OLs)are glial cells that myelinate axons with specialized lipid membrane extensions[2].OL progenitor cells(OPCs)arise from neural stem cells[3],and undergo proliferation before terminal differentiation and eventual myelination.Impairment at any stage of OL development can affect myelin formation.
文摘Myelin is an evolutionarily novel and important structure for the proper functioning of the vertebrate nervous system.In the central nervous system (CNS), the myelin sheath is elaborated by
基金supported by grants from High-level students returning to China (team) project in Hangzhou (2017)Zhejiang Provincial Natural Science Foundation of China (LY19C090002, LQ18C090005)Hangzhou Agriculture and Social Development Project (20191203B20)。
文摘Glioma is the most common type of tumor in the central nervous system, accounting for around 80% of all malignant brain tumors. Previous studies showed a significant association between nuclear morphology and the malignant progress of gliomas. By virtue of integrated proteomics and genomics analyses as well as experimental validations, we identify three nuclear lamin genes(LMNA, LMNB1, and LMNB2) that are significantly upregulated in glioma tissues compared with normal brain tissues. We show that elevated expressions of LMNB1, LMNB2, and LMNA in glioma cells are highly associated with the rapid progression of the disease and the knockdown of LMNB1, LMNB2, and LMNA dramatically suppresses glioma progression in both in vitro and in vivo mouse models. Moreover, the repression of glioma cell growth by lamin knockdown is mediated by the p Rb-mediated G1-S inhibition. On the contrary, overexpression of lamins in normal human astrocytes dramatically induced nuclear morphological aberrations and accelerated cell growth. Together, our multi-omics-based analysis has revealed a previously unrecognized role of lamin genes in gliomagenesis, providing a strong support for the key link between aberrant tumor nuclear shape and the survival of glioma patients. Based on these findings, lamins are proposed to be potential oncogene targets for therapeutic treatments of brain tumors.
基金supported by the National Natural Science Foundation of China (31771621,31171071 and 31671093)the Research Foundation for Advanced Talents from Hangzhou Normal University and the New York State Stem Cell Science contracts C026429 and C030133。
文摘Noxious mechanical information is transmitted through molecularly distinct nociceptors,with pinprickevoked sharp sensitivity via A-fiber nociceptors marked by developmental expression of the neuropeptide Y receptor 2(Npy2 r)and von Frey filament-evoked punctate pressure information via unmyelinated C fiber nociceptors marked by MrgprD.However,the molecular programs controlling their development are only beginning to be understood.Here we demonstrate that Npy2 r-expressing sensory neurons are in fact divided into two groups,based on transient or persistent Npy2 r expression.Npy2 r-transient neurons are myelinated,likely including A-fiber nociceptors,whereas Npy2 r-persistent ones belong to unmyelinated pruriceptors that co-express Nppb.We then showed that the transcription factors NFIA and Runx1 are necessary for the development of Npy2 r-transient A-fiber nociceptors and MrgprD^+C-fiber nociceptors,respectively.Behaviorally,mice with conditional knockout of Nfia,but not Runx1 showed a marked attenuation of pinprick-evoked nocifensive responses.Our studies therefore identify a transcription factor controlling the development of myelinated nociceptors.