Slowly dividing neural progenitors are an embryonic origin of adult neural stem cells

Shohei Furutachi; Hiroaki Miya; Tomoyuki Watanabe; Hiroki Kawai; Norihiko Yamasaki; Yujin Harada; Itaru Imayoshi; Mark Nelson; Keiichi I. Nakayama; Yusuke Hirabayashi; Yukiko Gotoh

doi:10.1038/nn.3989

Slowly dividing neural progenitors are an embryonic origin of adult neural stem cells

Shohei Furutachi, Hiroaki Miya, Tomoyuki Watanabe, Hiroki Kawai, Norihiko Yamasaki, Yujin Harada, Itaru Imayoshi, Mark Nelson, Keiichi I. Nakayama, Yusuke Hirabayashi, Yukiko Gotoh

Department of Molecular and Cellular Biology

Research output: Contribution to journal › Article › peer-review

197 Citations (Scopus)

Abstract

The mechanism by which adult neural stem cells (NSCs) are established during development is unclear. In this study, analysis of cell cycle progression by examining retention of a histone 2B (H2B)-GFP fusion protein revealed that, in a subset of mouse embryonic neural progenitor cells (NPCs), the cell cycle slows between embryonic day (E) 13.5 and E15.5 while other embryonic NPCs continue to divide rapidly. By allowing H2B-GFP expressed at E9.5 to become diluted in dividing cells until the young adult stage, we determined that a majority of NSCs in the young adult subependymal zone (SEZ) originated from these slowly dividing embryonic NPCs. The cyclin-dependent kinase inhibitor p57 is highly expressed in this embryonic subpopulation, and the deletion of p57 impairs the emergence of adult NSCs. Our results suggest that a substantial fraction of adult SEZ NSCs is derived from a slowly dividing subpopulation of embryonic NPCs and identify p57 as a key factor in generating this embryonic origin of adult SEZ NSCs.

Original language	English
Pages (from-to)	657-665
Number of pages	9
Journal	Nature Neuroscience
Volume	18
Issue number	5
DOIs	https://doi.org/10.1038/nn.3989
Publication status	Published - Apr 28 2015

All Science Journal Classification (ASJC) codes

Neuroscience(all)

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10.1038/nn.3989

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title = "Slowly dividing neural progenitors are an embryonic origin of adult neural stem cells",

abstract = "The mechanism by which adult neural stem cells (NSCs) are established during development is unclear. In this study, analysis of cell cycle progression by examining retention of a histone 2B (H2B)-GFP fusion protein revealed that, in a subset of mouse embryonic neural progenitor cells (NPCs), the cell cycle slows between embryonic day (E) 13.5 and E15.5 while other embryonic NPCs continue to divide rapidly. By allowing H2B-GFP expressed at E9.5 to become diluted in dividing cells until the young adult stage, we determined that a majority of NSCs in the young adult subependymal zone (SEZ) originated from these slowly dividing embryonic NPCs. The cyclin-dependent kinase inhibitor p57 is highly expressed in this embryonic subpopulation, and the deletion of p57 impairs the emergence of adult NSCs. Our results suggest that a substantial fraction of adult SEZ NSCs is derived from a slowly dividing subpopulation of embryonic NPCs and identify p57 as a key factor in generating this embryonic origin of adult SEZ NSCs.",

author = "Shohei Furutachi and Hiroaki Miya and Tomoyuki Watanabe and Hiroki Kawai and Norihiko Yamasaki and Yujin Harada and Itaru Imayoshi and Mark Nelson and Nakayama, {Keiichi I.} and Yusuke Hirabayashi and Yukiko Gotoh",

note = "Funding Information: We thank K. Tyssowski for editing the manuscript, F. Calegari (Center for Regenerative Therapies Dresden (CRTD)) for reagents, H. Sugizaki, C. Koga and J. Takeuchi for FACS analysis, A Shitamukai, F. Matsuzaki and Y. Sasai for comments and members of the Gotoh laboratory for discussion. This work was supported by Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Agency. Publisher Copyright: {\textcopyright} 2015 Nature America, Inc. All rights reserved.",

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AU - Furutachi, Shohei

AU - Miya, Hiroaki

AU - Watanabe, Tomoyuki

AU - Kawai, Hiroki

AU - Yamasaki, Norihiko

AU - Harada, Yujin

AU - Imayoshi, Itaru

AU - Nelson, Mark

AU - Nakayama, Keiichi I.

AU - Hirabayashi, Yusuke

AU - Gotoh, Yukiko

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PY - 2015/4/28

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N2 - The mechanism by which adult neural stem cells (NSCs) are established during development is unclear. In this study, analysis of cell cycle progression by examining retention of a histone 2B (H2B)-GFP fusion protein revealed that, in a subset of mouse embryonic neural progenitor cells (NPCs), the cell cycle slows between embryonic day (E) 13.5 and E15.5 while other embryonic NPCs continue to divide rapidly. By allowing H2B-GFP expressed at E9.5 to become diluted in dividing cells until the young adult stage, we determined that a majority of NSCs in the young adult subependymal zone (SEZ) originated from these slowly dividing embryonic NPCs. The cyclin-dependent kinase inhibitor p57 is highly expressed in this embryonic subpopulation, and the deletion of p57 impairs the emergence of adult NSCs. Our results suggest that a substantial fraction of adult SEZ NSCs is derived from a slowly dividing subpopulation of embryonic NPCs and identify p57 as a key factor in generating this embryonic origin of adult SEZ NSCs.

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Slowly dividing neural progenitors are an embryonic origin of adult neural stem cells

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