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Neural stem/precursor cells dynamically change their epigenetic landscape to differentially respond to BMP signaling for fate switching during brain development
During neocortical development, tight regulation of neurogenesis-to-astrogenesis switching of neural precursor cells (NPCs) is critical to generate a balanced number of each neural cell type for proper brain functions. Accumulating evidence indicates that a complex array of epigenetic modifications...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559679/ https://www.ncbi.nlm.nih.gov/pubmed/34675062 http://dx.doi.org/10.1101/gad.348797.121 |
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author | Katada, Sayako Takouda, Jun Nakagawa, Takumi Honda, Mizuki Igarashi, Katsuhide Imamura, Takuya Ohkawa, Yasuyuki Sato, Shoko Kurumizaka, Hitoshi Nakashima, Kinichi |
author_facet | Katada, Sayako Takouda, Jun Nakagawa, Takumi Honda, Mizuki Igarashi, Katsuhide Imamura, Takuya Ohkawa, Yasuyuki Sato, Shoko Kurumizaka, Hitoshi Nakashima, Kinichi |
author_sort | Katada, Sayako |
collection | PubMed |
description | During neocortical development, tight regulation of neurogenesis-to-astrogenesis switching of neural precursor cells (NPCs) is critical to generate a balanced number of each neural cell type for proper brain functions. Accumulating evidence indicates that a complex array of epigenetic modifications and the availability of extracellular factors control the timing of neuronal and astrocytic differentiation. However, our understanding of NPC fate regulation is still far from complete. Bone morphogenetic proteins (BMPs) are renowned as cytokines that induce astrogenesis of gliogenic late-gestational NPCs. They also promote neurogenesis of mid-gestational NPCs, although the underlying mechanisms remain elusive. By performing multiple genome-wide analyses, we demonstrate that Smads, transcription factors that act downstream from BMP signaling, target dramatically different genomic regions in neurogenic and gliogenic NPCs. We found that histone H3K27 trimethylation and DNA methylation around Smad-binding sites change rapidly as gestation proceeds, strongly associated with the alteration of accessibility of Smads to their target binding sites. Furthermore, we identified two lineage-specific Smad-interacting partners—Sox11 for neurogenic and Sox8 for astrocytic differentiation—that further ensure Smad-regulated fate-specific gene induction. Our findings illuminate an exquisite regulation of NPC property change mediated by the interplay between cell-extrinsic cues and -intrinsic epigenetic programs during cortical development. |
format | Online Article Text |
id | pubmed-8559679 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-85596792021-11-10 Neural stem/precursor cells dynamically change their epigenetic landscape to differentially respond to BMP signaling for fate switching during brain development Katada, Sayako Takouda, Jun Nakagawa, Takumi Honda, Mizuki Igarashi, Katsuhide Imamura, Takuya Ohkawa, Yasuyuki Sato, Shoko Kurumizaka, Hitoshi Nakashima, Kinichi Genes Dev Research Paper During neocortical development, tight regulation of neurogenesis-to-astrogenesis switching of neural precursor cells (NPCs) is critical to generate a balanced number of each neural cell type for proper brain functions. Accumulating evidence indicates that a complex array of epigenetic modifications and the availability of extracellular factors control the timing of neuronal and astrocytic differentiation. However, our understanding of NPC fate regulation is still far from complete. Bone morphogenetic proteins (BMPs) are renowned as cytokines that induce astrogenesis of gliogenic late-gestational NPCs. They also promote neurogenesis of mid-gestational NPCs, although the underlying mechanisms remain elusive. By performing multiple genome-wide analyses, we demonstrate that Smads, transcription factors that act downstream from BMP signaling, target dramatically different genomic regions in neurogenic and gliogenic NPCs. We found that histone H3K27 trimethylation and DNA methylation around Smad-binding sites change rapidly as gestation proceeds, strongly associated with the alteration of accessibility of Smads to their target binding sites. Furthermore, we identified two lineage-specific Smad-interacting partners—Sox11 for neurogenic and Sox8 for astrocytic differentiation—that further ensure Smad-regulated fate-specific gene induction. Our findings illuminate an exquisite regulation of NPC property change mediated by the interplay between cell-extrinsic cues and -intrinsic epigenetic programs during cortical development. Cold Spring Harbor Laboratory Press 2021-11-01 /pmc/articles/PMC8559679/ /pubmed/34675062 http://dx.doi.org/10.1101/gad.348797.121 Text en © 2021 Katada et al.; Published by Cold Spring Harbor Laboratory Press https://creativecommons.org/licenses/by-nc/4.0/This article, published in Genes & Development, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Research Paper Katada, Sayako Takouda, Jun Nakagawa, Takumi Honda, Mizuki Igarashi, Katsuhide Imamura, Takuya Ohkawa, Yasuyuki Sato, Shoko Kurumizaka, Hitoshi Nakashima, Kinichi Neural stem/precursor cells dynamically change their epigenetic landscape to differentially respond to BMP signaling for fate switching during brain development |
title | Neural stem/precursor cells dynamically change their epigenetic landscape to differentially respond to BMP signaling for fate switching during brain development |
title_full | Neural stem/precursor cells dynamically change their epigenetic landscape to differentially respond to BMP signaling for fate switching during brain development |
title_fullStr | Neural stem/precursor cells dynamically change their epigenetic landscape to differentially respond to BMP signaling for fate switching during brain development |
title_full_unstemmed | Neural stem/precursor cells dynamically change their epigenetic landscape to differentially respond to BMP signaling for fate switching during brain development |
title_short | Neural stem/precursor cells dynamically change their epigenetic landscape to differentially respond to BMP signaling for fate switching during brain development |
title_sort | neural stem/precursor cells dynamically change their epigenetic landscape to differentially respond to bmp signaling for fate switching during brain development |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559679/ https://www.ncbi.nlm.nih.gov/pubmed/34675062 http://dx.doi.org/10.1101/gad.348797.121 |
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