Transcriptional Profiling of Hypoxic Neural Stem Cells Identifies Calcineurin-NFATc4 Signaling as a Major Regulator of Neural Stem Cell Biology
نویسندگان
چکیده
Neural stem cells (NSCs) reside in a hypoxic microenvironment within the brain. However, the crucial transcription factors (TFs) that regulate NSC biology under physiologic hypoxia are poorly understood. Here we have performed gene set enrichment analysis (GSEA) of microarray datasets from hypoxic versus normoxic NSCs with the aim of identifying pathways and TFs that are activated under oxygen concentrations mimicking normal brain tissue microenvironment. Integration of TF target (TFT) and pathway enrichment analysis identified the calcium-regulated TF NFATc4 as a major candidate to regulate hypoxic NSC functions. Nfatc4 expression was coordinately upregulated by top hypoxia-activated TFs, while NFATc4 target genes were enriched in hypoxic NSCs. Loss-of-function analyses further revealed that the calcineurin-NFATc4 signaling axis acts as a major regulator of NSC self-renewal and proliferation in vitro and in vivo by promoting the expression of TFs, including Id2, that contribute to the maintenance of the NSC state.
منابع مشابه
Analysis of Promyelocytic Leukemia in Human Embryonic Carcinoma Stem Cells During Retinoic Acid-Induced Neural Differentiation
Background: Promyelocytic leukemia protein (PML) is a tumor suppressor protein that is involved in myeloid cell differentiation in response to retinoic acid (RA). In addition, RA acts as a natural morphogen in neural development. Objectives: This study aimed to examine PML gene expression in different stages of in vitro neural differentiation of NT2 cells, and to investigate the possible role o...
متن کاملAlpha-Tocopherol increases the proliferation of induced pluripotent stem cell derived neural progenitor cells
In addition to its antioxidant effect, Vitamin E or α–tocopherol is suggested to enhance remyelination in the animal model of non-inflammatory demyelination. In this study, the possible proliferative effect of vitamin E on human- induced pluripotent stem cell-derived neural progenitors (hiPS-NPs) and the underlying mechanisms were investigated in vitro. NPs were induced from iPS cells via 3 ste...
متن کاملFingolimod Enhances Oligodendrocyte Differentiation of Transplanted Human Induced Pluripotent Stem Cell-Derived Neural Progenitors
Multiple sclerosis (MS) is an autoimmune disease which affects myelin in the central nervous system (CNS) and leads to serious disability. Currently available treatments for MS mainly suppress the immune system. Regenerative medicine-based approaches attempt to increase myelin repair by targeting endogenous progenitors or transplanting stem cells or their derivatives. Fingolimod exerts anti-inf...
متن کاملFingolimod Enhances Oligodendrocyte Differentiation of Transplanted Human Induced Pluripotent Stem Cell-Derived Neural Progenitors
Multiple sclerosis (MS) is an autoimmune disease which affects myelin in the central nervous system (CNS) and leads to serious disability. Currently available treatments for MS mainly suppress the immune system. Regenerative medicine-based approaches attempt to increase myelin repair by targeting endogenous progenitors or transplanting stem cells or their derivatives. Fingolimod exerts anti-inf...
متن کاملDifferentiation of Mouse Stem Cells into Neural Cells on PLGA Microspheres Scaffold
The cellular therapy and nerve tissue engineering will probably become a major therapeutic strategy for promoting axonal growth through injured area in central nervous system and peripheral nervous system in the coming years. The stem cell carrier scaffolds in nerve tissue engineering resulted in strong survival of cells and suitable differentiation into n...
متن کامل