TY - JOUR
T1 - Neural stem/precursor cells dynamically change their epigenetic landscape to differentially respond to BMP signaling for fate switching during brain development
AU - Katada, Sayako
AU - Takouda, Jun
AU - Nakagawa, Takumi
AU - Honda, Mizuki
AU - Igarashi, Katsuhide
AU - Imamura, Takuya
AU - Ohkawa, Yasuyuki
AU - Sato, Shoko
AU - Kurumizaka, Hitoshi
AU - Nakashima, Kinichi
N1 - Funding Information:
We thank M.E. Greenberg for pLLX vector, H. Kimura for antiH3K27me3 antibodies, and I. Smith for proofreading the manuscript. We appreciate technical assistance from the Research Support Center, Kyushu University Graduate School of Medical Sciences. We thank N. Yamamoto and M. Otsuka for technical advice for NGS. This work was supported by The Ministry of Education, Culture, Sports, Science, and Technology/Japan Society for the Promotion of Science KAKENHI (JP16H06527 and JP16K21734 to K.N., and JP26710003 and JP20K06875 to S.K.), Japan Science and Technology Agency CREST (JPMJCR16G1 to Y.O. and H.K.), the Naito Foundation (S.K.), and the Platform for Advanced Genome Science (PAGS; JP17H05647 to S.K.).
Funding Information:
We thank M.E. Greenberg for pLLX vector, H. Kimura for anti-H3K27me3 antibodies, and I. Smith for proofreading the manuscript. We appreciate technical assistance from the Research Support Center, Kyushu University Graduate School of Medical Sciences. We thank N. Yamamoto and M. Otsuka for technical advice for NGS. This work was supported by The Ministry of Education, Culture, Sports, Science, and Technology/Japan Society for the Promotion of Science KAKENHI (JP16H06527 and JP16K21734 to K.N., and JP26710003 and JP20K06875 to S.K.), Japan Science and Technology Agency CREST (JPMJCR16G1 to Y.O. and H.K.), the Naito Foundation (S.K.), and the Platform for Advanced Genome Science (PAGS; JP17H05647 to S.K.).
Publisher Copyright:
© 2021 Katada et al. 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/.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - 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.
AB - 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.
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U2 - 10.1101/GAD.348797.121
DO - 10.1101/GAD.348797.121
M3 - Article
C2 - 34675062
AN - SCOPUS:85119355367
VL - 35
SP - 1431
EP - 1444
JO - Genes and Development
JF - Genes and Development
SN - 0890-9369
IS - 21-22
ER -