The role of type-2 astrocytes in the repair of central nervous system injury remains poorly un- derstood. In this study, using a relatively simple culture condition in vitro, type-2 astrocytes, differentiated from oli...The role of type-2 astrocytes in the repair of central nervous system injury remains poorly un- derstood. In this study, using a relatively simple culture condition in vitro, type-2 astrocytes, differentiated from oligodendrocyte precursor cells by induction with bone morphogenetic pro- tein-4, were co-cultured with dorsal root ganglion neurons. We examined the effects of type-2 astrocytes differentiated from oligodendrocyte precursor cells on the survival and growth of dorsal root ganglion neurons. Results demonstrated that the number of dorsal root ganglion neurons was higher following co-culture of oligodendrocyte precursor cells and type-2 astrocytes than when cultured alone, but lower than that of neurons co-cultured with type-1 astrocytes. The length of the longest process and the length of all processes of a single neuron were shortest in neurons cultured alone, followed by neurons co-cultured with type-2 astroc^es, then neurons co-cultured with oligodendrocyte precursor cells, and longest in neurons co-cultured with type-1 astrocytes. These results indicate that co-culture with type-2 astrocytes can increase neuronal survival rate and process length. However, compared with type-1 astrocytes and oligodendrocyte precursor cells, the promotion effects of type-2 astrocytes on the growth of dorsal root ganglion neurons were weaker.展开更多
Alternative splicing(AS) is an essential mechanism in post-transcriptional regulation and leads to protein diversity. It has been shown that AS is prevalent in metazoan genomes, and the splicing pattern is dynamically...Alternative splicing(AS) is an essential mechanism in post-transcriptional regulation and leads to protein diversity. It has been shown that AS is prevalent in metazoan genomes, and the splicing pattern is dynamically regulated in different tissues and cell types, including embryonic stem cells. These observations suggest that AS may play critical roles in stem cell biology. Since embryonic stem cells and induced pluripotent stem cells have the ability to give rise to alltypes of cells and tissues, they hold the promise of future cell-based therapy. Many efforts have been devoted to understanding the mechanisms underlying stem cell selfrenewal and differentiation. However, most of the studies focused on the expression of a core set of transcription factors and regulatory RNAs. The role of AS in stem cell differentiation was not clear. Recent advances in highthroughput technologies have all owed the profiling of dynamic splicing patterns and cis-motifs that are responsible for AS at a genome-wide scale, and provided novel insights in a number of studies. In this review, we discuss some recent findings involving AS and stem cells. An emerging picture from these findings is that AS is integrated in the transcriptional and post-transcriptional networks and together they control pluripotency maintenance and differentiation of stem cells.展开更多
GUoma is a complex disease with limited treatment options. Recent advances have identified isocitrate dehydrogenase （IDH） mutations in up to 80% lower grade gUomas （LGG） and in 76% secondary gUoblastomas （GBM）. ...GUoma is a complex disease with limited treatment options. Recent advances have identified isocitrate dehydrogenase （IDH） mutations in up to 80% lower grade gUomas （LGG） and in 76% secondary gUoblastomas （GBM）. IDH mutations are also seen in 10%-20% of acute myeloid leukemia （AML）. In AML, it was determined that mutations of IDH and other genes involving epigenetic regulations are early events, emerging in the pre-leukemic stem cells （pre-LSCs） stage, whereas mutations in genes propa- gating oncogenic signal are late events in leukemia. IDH mutations are also early events in gUoma, occurring before TP53 mutation, 1p/19q deletion, etc. Despite these advances in gUoma research, studies into other molecular alterations have lagged considerably. In this study, we analyzed currently available databases. We identified EZH2, KMT2C, and CHD# as important genes in glioma in addition to the known gene IDH1/2. We also showed that genomic alterations of PIK3CA, CDKN2A, CDK#, FIPIL1, or FUBP1 collaborate with IDH mutations to negatively affect patients＇ survival in LGG. In LGG patients with TP53 mutations or IDH1/2 mutations, additional genomic alterations of EZH2, KMC2C, and CHD4 individually or in combination were associated with a markedly decreased disease-free survival than patients without such alterations. Alterations of EZH2, KMT2C, and CHD4, at gen- etic level or protein level could perturb epigenetic program, leading to malignant transformation in glioma. By reviewing current literature on both AML and gUoma and performing bioinformatics analysis on available datasets, we developed a hypothetical model on the tumorigenesis from premaUgnant stem cells to gUoma.展开更多
基金supported by the NIH Foundation of the USA,No.R01 NS061975the Natural Science Foundation of Hunan Province in China,No.11JJ6077
文摘The role of type-2 astrocytes in the repair of central nervous system injury remains poorly un- derstood. In this study, using a relatively simple culture condition in vitro, type-2 astrocytes, differentiated from oligodendrocyte precursor cells by induction with bone morphogenetic pro- tein-4, were co-cultured with dorsal root ganglion neurons. We examined the effects of type-2 astrocytes differentiated from oligodendrocyte precursor cells on the survival and growth of dorsal root ganglion neurons. Results demonstrated that the number of dorsal root ganglion neurons was higher following co-culture of oligodendrocyte precursor cells and type-2 astrocytes than when cultured alone, but lower than that of neurons co-cultured with type-1 astrocytes. The length of the longest process and the length of all processes of a single neuron were shortest in neurons cultured alone, followed by neurons co-cultured with type-2 astroc^es, then neurons co-cultured with oligodendrocyte precursor cells, and longest in neurons co-cultured with type-1 astrocytes. These results indicate that co-culture with type-2 astrocytes can increase neuronal survival rate and process length. However, compared with type-1 astrocytes and oligodendrocyte precursor cells, the promotion effects of type-2 astrocytes on the growth of dorsal root ganglion neurons were weaker.
文摘Alternative splicing(AS) is an essential mechanism in post-transcriptional regulation and leads to protein diversity. It has been shown that AS is prevalent in metazoan genomes, and the splicing pattern is dynamically regulated in different tissues and cell types, including embryonic stem cells. These observations suggest that AS may play critical roles in stem cell biology. Since embryonic stem cells and induced pluripotent stem cells have the ability to give rise to alltypes of cells and tissues, they hold the promise of future cell-based therapy. Many efforts have been devoted to understanding the mechanisms underlying stem cell selfrenewal and differentiation. However, most of the studies focused on the expression of a core set of transcription factors and regulatory RNAs. The role of AS in stem cell differentiation was not clear. Recent advances in highthroughput technologies have all owed the profiling of dynamic splicing patterns and cis-motifs that are responsible for AS at a genome-wide scale, and provided novel insights in a number of studies. In this review, we discuss some recent findings involving AS and stem cells. An emerging picture from these findings is that AS is integrated in the transcriptional and post-transcriptional networks and together they control pluripotency maintenance and differentiation of stem cells.
文摘GUoma is a complex disease with limited treatment options. Recent advances have identified isocitrate dehydrogenase （IDH） mutations in up to 80% lower grade gUomas （LGG） and in 76% secondary gUoblastomas （GBM）. IDH mutations are also seen in 10%-20% of acute myeloid leukemia （AML）. In AML, it was determined that mutations of IDH and other genes involving epigenetic regulations are early events, emerging in the pre-leukemic stem cells （pre-LSCs） stage, whereas mutations in genes propa- gating oncogenic signal are late events in leukemia. IDH mutations are also early events in gUoma, occurring before TP53 mutation, 1p/19q deletion, etc. Despite these advances in gUoma research, studies into other molecular alterations have lagged considerably. In this study, we analyzed currently available databases. We identified EZH2, KMT2C, and CHD# as important genes in glioma in addition to the known gene IDH1/2. We also showed that genomic alterations of PIK3CA, CDKN2A, CDK#, FIPIL1, or FUBP1 collaborate with IDH mutations to negatively affect patients＇ survival in LGG. In LGG patients with TP53 mutations or IDH1/2 mutations, additional genomic alterations of EZH2, KMC2C, and CHD4 individually or in combination were associated with a markedly decreased disease-free survival than patients without such alterations. Alterations of EZH2, KMT2C, and CHD4, at gen- etic level or protein level could perturb epigenetic program, leading to malignant transformation in glioma. By reviewing current literature on both AML and gUoma and performing bioinformatics analysis on available datasets, we developed a hypothetical model on the tumorigenesis from premaUgnant stem cells to gUoma.
