The stem cells of an organism only possess extraordinary capacity to change into different cell types during the early life and growth of an organism. When these stem cells divide into different new cells, these eithe...The stem cells of an organism only possess extraordinary capacity to change into different cell types during the early life and growth of an organism. When these stem cells divide into different new cells, these either remain as stem cells or develop to become other cells with specialized function. For this reason, stem cells offer direct relevance to human health, as theoretically, using stem cell technology, different organs are expected to be regenerated. To this, the Human Embryonic Stem Cells (HESCs) are natural pluripotent cell, but ethical issues covering many countries have put research work on a bit back-foot. However, the Induced Pluripotent Stem Cells (iPSCs) technology has completely revitalized the world to use this technology universally and it therefore seems that more research on this technology will surely be of enormous help in public health. In addition, application of the stem cell technology in personalized-medicine has been started recently. In this concern, the stem cell banking facilities have provided new avenues for preserving the cord blood of the new-borne child and treat them in future by using her/his own preserved stem cells. However, like all new technologies, the output from stem cell research requires to be evaluated more closely. Furthermore, with proper guidelines on ethical issues and extended research following these strategies, the stem cell technology is expected to not only be of huge benefit to human health, but also the benefit can be extended to the survival of endangered animals as well.展开更多
Air pollution has been linked to many health issues,including skin conditions,especially in children.Among all the atmospheric pollutants,ultrafine particles have been deemed very dangerous since they can readily pene...Air pollution has been linked to many health issues,including skin conditions,especially in children.Among all the atmospheric pollutants,ultrafine particles have been deemed very dangerous since they can readily penetrate the lungs and skin,and be absorbed into the bloodstream.Here,we employed a human embryonic stem cell(h ESC)-based differentiation system towards keratinocytes,to test the effects of ultrafine carbon particles,which mimic ambient ultrafine particles,at environment related concentrations.We found that10 ng/mL to 10μg/mL ultrafine carbon particles down-regulated the expression of the pluripotency marker SOX2 in h ESCs.Moreover,1μg/mL to 10μg/mL carbon particle treatments disrupted the keratinocyte differentiation,and up-regulated inflammationand psoriasis-related genes,such as IL-1β,IL-6,CXCL1,CXCL2,CXCL3,CCL20,CXCL8,and S100 A7 and S100 A9,respectively.Overall,our results provide a new insight into the potential developmental toxicity of atmospheric ultrafine particles.展开更多
The pluripotent state between human and mouse embryonic stem cells is different.Pluripotent state of human embryonic stem cells(ESCs)is believed to be primed and is similar with that of mouse epiblast stem cells(EpiSC...The pluripotent state between human and mouse embryonic stem cells is different.Pluripotent state of human embryonic stem cells(ESCs)is believed to be primed and is similar with that of mouse epiblast stem cells(EpiSCs),which is different from the naïve state of mouse ESCs.Human ESCs could be converted into a naïve state through exogenous expression of defined transcription factors(Hanna et al.,2010).Here we report a rapid conversion of human ESCs to mouse ESC-like naïve states only by modifying the culture conditions.These converted human ESCs,which we called mhESCs(mouse ESC-like human ESCs),have normal karyotype,allow single cell passage,exhibit domed morphology like mouse ESCs and express some pluripotent markers similar with mouse ESCs.Thus the rapid conversion established a naïve pluripotency in human ESCs like mouse ESCs,and provided a new model to study the regulation of pluripotency.展开更多
Human embryonic stem cells(hESCs)are pluripotent cells that have the ability of unlimited self-renewal and can be differentiated into different cell lineages,includ-ing neural stem(NS)cells.Diverse regulatory signalin...Human embryonic stem cells(hESCs)are pluripotent cells that have the ability of unlimited self-renewal and can be differentiated into different cell lineages,includ-ing neural stem(NS)cells.Diverse regulatory signaling pathways of neural stem cells differentiation have been discovered,and this will be of great benefit to uncover the mechanisms of neuronal differentiation in vivo and in vitro.However,the limitations of hESCs resource along with the religious and ethical concerns impede the pro-gress of ESCs application.Therefore,the induced pluri-potent stem cells(iPSCs)via somatic cell reprogramming have opened up another new territory for regenerative medicine.iPSCs now can be derived from a number of lin-eages of cells,and are able to differentiate into certain cell types,including neurons.Patient-specifi c iPSCs are being used in human neurodegenerative disease modeling and drug screening.Furthermore,with the development of somatic direct reprogramming or lineage reprogramming technique,a more effective approach for regenerative medicine could become a complement for iPSCs.展开更多
The hematopoietic function of HOXC4 has not been extensively investigated.Our research indicated that induction of HOXC4 in co-culture system from D10 significantly promoted productions of most hematopoietic progenito...The hematopoietic function of HOXC4 has not been extensively investigated.Our research indicated that induction of HOXC4 in co-culture system from D10 significantly promoted productions of most hematopoietic progenitor cells.CD34−CD43+cells could be clearly classified into CD34−CD43^(low) and CD34−CD43^(high) sub-populations at D14.The former cells had greater myelogenic potential,and their production was not significantly influenced by induction of HOXC4.By contrast,the latter cells had greater potential to differentiate into megakaryocytes and erythroid cells,and thus had properties of erythroid–megakaryocyte common progenitors,which abundance was increased by∼2-fold when HOXC4 was induced from D10.For CD34−CD43^(low),CD34+CD43+,and CD34−CD43^(high) sub-populations,CD43 level served as a natural index for the tendency to undergo hematopoiesis.Induction of HOXC4 from D10 caused more CD43+cells sustain in S-phase with up-regulation of NF-κB signaling,which could be counteracted by inhibition of NF-κB signaling.These observations suggested that promotion of hematopoiesis by HOXC4 is closely related to NF-κB signaling and a change in cell-cycle status,which containing potential of clinical applications.展开更多
Background: The HOX genes are master regulators of embryogenesis that are also involved inhematopoiesis. HOXA9 belongs to a cluster of HOX genes that play extensively studied roles inhematopoiesis and leukemogenesis.M...Background: The HOX genes are master regulators of embryogenesis that are also involved inhematopoiesis. HOXA9 belongs to a cluster of HOX genes that play extensively studied roles inhematopoiesis and leukemogenesis.Methods: We established HOXA9-inducible human embryonic stem cells (HOXA9/hESCs) with normalpluripotency and potential for hematopoiesis, which could be used to analyze gene function with highaccuracy. HOXA9/hESCs co-cultured with aorta–gonad–mesonephros-derived stromal cells (AGM-S3) wereinduced to overexpress HOXA9 with doxycycline (DOX) at various times after hematopoiesis started andthen subjected to flow cytometry.Results: Induction of HOXA9 from Day 4 (D4) or later notably promoted hematopoiesis and also increasedthe production of CD34+ cells and derived populations. The potential for myelogenesis was significantlyelevated while the potential for erythrogenesis was significantly reduced. At D14, a significant promotion ofS phase was observed in green fluorescent protein positive (GFP+) cells overexpressing HOXA9. NF-κBsignaling was also up-regulated at D14 following induction of HOXA9 on D4. All of these effects could becounteracted by addition of an NF-κB inhibitor or siRNA against NFKB1 along with DOX.Conclusions: Overexpression of HOXA9 starting at D4 or later during hematopoiesis significantly promotedhematopoiesis and the production of myeloid progenitors while reduced the production of erythroidprogenitors, indicating that HOXA9 plays a key role in hematopoiesis and differentiation of hematopoieticlineages.展开更多
文摘The stem cells of an organism only possess extraordinary capacity to change into different cell types during the early life and growth of an organism. When these stem cells divide into different new cells, these either remain as stem cells or develop to become other cells with specialized function. For this reason, stem cells offer direct relevance to human health, as theoretically, using stem cell technology, different organs are expected to be regenerated. To this, the Human Embryonic Stem Cells (HESCs) are natural pluripotent cell, but ethical issues covering many countries have put research work on a bit back-foot. However, the Induced Pluripotent Stem Cells (iPSCs) technology has completely revitalized the world to use this technology universally and it therefore seems that more research on this technology will surely be of enormous help in public health. In addition, application of the stem cell technology in personalized-medicine has been started recently. In this concern, the stem cell banking facilities have provided new avenues for preserving the cord blood of the new-borne child and treat them in future by using her/his own preserved stem cells. However, like all new technologies, the output from stem cell research requires to be evaluated more closely. Furthermore, with proper guidelines on ethical issues and extended research following these strategies, the stem cell technology is expected to not only be of huge benefit to human health, but also the benefit can be extended to the survival of endangered animals as well.
基金supported by the National Natural Science Foundation of China(Nos.21876197,21577166,21707160)the Chinese Academy of Sciences(Nos.XDB14040301,QYZDJSSW-DQC017)the K.C.Wong Education Foundation
文摘Air pollution has been linked to many health issues,including skin conditions,especially in children.Among all the atmospheric pollutants,ultrafine particles have been deemed very dangerous since they can readily penetrate the lungs and skin,and be absorbed into the bloodstream.Here,we employed a human embryonic stem cell(h ESC)-based differentiation system towards keratinocytes,to test the effects of ultrafine carbon particles,which mimic ambient ultrafine particles,at environment related concentrations.We found that10 ng/mL to 10μg/mL ultrafine carbon particles down-regulated the expression of the pluripotency marker SOX2 in h ESCs.Moreover,1μg/mL to 10μg/mL carbon particle treatments disrupted the keratinocyte differentiation,and up-regulated inflammationand psoriasis-related genes,such as IL-1β,IL-6,CXCL1,CXCL2,CXCL3,CCL20,CXCL8,and S100 A7 and S100 A9,respectively.Overall,our results provide a new insight into the potential developmental toxicity of atmospheric ultrafine particles.
基金by grants from the China National Basic Research Program(Grant No.2011CB965300)to L.W.grants from the National Natural Science Foundation of China(Grant No.90919060)to Q.Z.grants from the"Strategic Priority Research Program"of the Chinese Academy of Sciences(No.XDA01020101)to Q.Z.
文摘The pluripotent state between human and mouse embryonic stem cells is different.Pluripotent state of human embryonic stem cells(ESCs)is believed to be primed and is similar with that of mouse epiblast stem cells(EpiSCs),which is different from the naïve state of mouse ESCs.Human ESCs could be converted into a naïve state through exogenous expression of defined transcription factors(Hanna et al.,2010).Here we report a rapid conversion of human ESCs to mouse ESC-like naïve states only by modifying the culture conditions.These converted human ESCs,which we called mhESCs(mouse ESC-like human ESCs),have normal karyotype,allow single cell passage,exhibit domed morphology like mouse ESCs and express some pluripotent markers similar with mouse ESCs.Thus the rapid conversion established a naïve pluripotency in human ESCs like mouse ESCs,and provided a new model to study the regulation of pluripotency.
基金the National Basic Research Program 973 program(No.2012CB966800)the Thousand Youth Talents Program and the Pioneer Programs of Chinese Academy of Sciences。
文摘Human embryonic stem cells(hESCs)are pluripotent cells that have the ability of unlimited self-renewal and can be differentiated into different cell lineages,includ-ing neural stem(NS)cells.Diverse regulatory signaling pathways of neural stem cells differentiation have been discovered,and this will be of great benefit to uncover the mechanisms of neuronal differentiation in vivo and in vitro.However,the limitations of hESCs resource along with the religious and ethical concerns impede the pro-gress of ESCs application.Therefore,the induced pluri-potent stem cells(iPSCs)via somatic cell reprogramming have opened up another new territory for regenerative medicine.iPSCs now can be derived from a number of lin-eages of cells,and are able to differentiate into certain cell types,including neurons.Patient-specifi c iPSCs are being used in human neurodegenerative disease modeling and drug screening.Furthermore,with the development of somatic direct reprogramming or lineage reprogramming technique,a more effective approach for regenerative medicine could become a complement for iPSCs.
基金This work was supported by awards from the CAMS Initiatives for Innovative Medicine(2016-I2M-1-018 to F.Ma and 2017-I2M-3-021 to J.X.Liu)Sichuan Provincial Science and Technology Department Key R&D projects(020YFSY0023 to B.Chen)the Chengdu Science and Technology Project-Technology Innovation R&D(2018-YF05-01341-SN to B.Chen).
文摘The hematopoietic function of HOXC4 has not been extensively investigated.Our research indicated that induction of HOXC4 in co-culture system from D10 significantly promoted productions of most hematopoietic progenitor cells.CD34−CD43+cells could be clearly classified into CD34−CD43^(low) and CD34−CD43^(high) sub-populations at D14.The former cells had greater myelogenic potential,and their production was not significantly influenced by induction of HOXC4.By contrast,the latter cells had greater potential to differentiate into megakaryocytes and erythroid cells,and thus had properties of erythroid–megakaryocyte common progenitors,which abundance was increased by∼2-fold when HOXC4 was induced from D10.For CD34−CD43^(low),CD34+CD43+,and CD34−CD43^(high) sub-populations,CD43 level served as a natural index for the tendency to undergo hematopoiesis.Induction of HOXC4 from D10 caused more CD43+cells sustain in S-phase with up-regulation of NF-κB signaling,which could be counteracted by inhibition of NF-κB signaling.These observations suggested that promotion of hematopoiesis by HOXC4 is closely related to NF-κB signaling and a change in cell-cycle status,which containing potential of clinical applications.
基金This work was supported by awards from the CAMS Initiatives for Innovative Medicine(2016-I2M-1-018 to F.Ma and 2017-I2M-3-021 to J.X.Liu)Sichuan Provincial Science and Technology Department Key R&D projects(020YFSY0023 to B.Chen)the Chengdu Science and Technology Project-Technology Innovation R&D(2018-YF05-01341-SN to B.Chen).
文摘Background: The HOX genes are master regulators of embryogenesis that are also involved inhematopoiesis. HOXA9 belongs to a cluster of HOX genes that play extensively studied roles inhematopoiesis and leukemogenesis.Methods: We established HOXA9-inducible human embryonic stem cells (HOXA9/hESCs) with normalpluripotency and potential for hematopoiesis, which could be used to analyze gene function with highaccuracy. HOXA9/hESCs co-cultured with aorta–gonad–mesonephros-derived stromal cells (AGM-S3) wereinduced to overexpress HOXA9 with doxycycline (DOX) at various times after hematopoiesis started andthen subjected to flow cytometry.Results: Induction of HOXA9 from Day 4 (D4) or later notably promoted hematopoiesis and also increasedthe production of CD34+ cells and derived populations. The potential for myelogenesis was significantlyelevated while the potential for erythrogenesis was significantly reduced. At D14, a significant promotion ofS phase was observed in green fluorescent protein positive (GFP+) cells overexpressing HOXA9. NF-κBsignaling was also up-regulated at D14 following induction of HOXA9 on D4. All of these effects could becounteracted by addition of an NF-κB inhibitor or siRNA against NFKB1 along with DOX.Conclusions: Overexpression of HOXA9 starting at D4 or later during hematopoiesis significantly promotedhematopoiesis and the production of myeloid progenitors while reduced the production of erythroidprogenitors, indicating that HOXA9 plays a key role in hematopoiesis and differentiation of hematopoieticlineages.
