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  1. B200 工学部/工学研究科
  2. B200a 雑誌掲載論文
  3. 学術雑誌

Time Scales in Epigenetic Dynamics and Phenotypic Heterogeneity of Embryonic Stem Cells

http://hdl.handle.net/2237/20624
http://hdl.handle.net/2237/20624
c3752295-27cd-4f09-9dbd-5f3d1fb0e274
名前 / ファイル ライセンス アクション
journal_pcbi_1003380.pdf journal_pcbi_1003380.pdf (3.1 MB)
Item type 学術雑誌論文 / Journal Article(1)
公開日 2014-10-30
タイトル
タイトル Time Scales in Epigenetic Dynamics and Phenotypic Heterogeneity of Embryonic Stem Cells
言語 en
著者 Sasai, Masaki

× Sasai, Masaki

WEKO 53852

en Sasai, Masaki

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Kawabata, Yudai

× Kawabata, Yudai

WEKO 53853

en Kawabata, Yudai

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Makishi, Koh

× Makishi, Koh

WEKO 53854

en Makishi, Koh

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Itoh, Kazuhito

× Itoh, Kazuhito

WEKO 53855

en Itoh, Kazuhito

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Terada, Tomoki P.

× Terada, Tomoki P.

WEKO 53856

en Terada, Tomoki P.

Search repository
アクセス権
アクセス権 open access
アクセス権URI http://purl.org/coar/access_right/c_abf2
抄録
内容記述 A remarkable feature of the self-renewing population of embryonic stem cells (ESCs) is their phenotypic heterogeneity: Nanog and other marker proteins of ESCs show large cell-to-cell variation in their expression level, which should significantly influence the differentiation process of individual cells. The molecular mechanism and biological implication of this heterogeneity, however, still remain elusive. We address this problem by constructing a model of the core gene-network of mouse ESCs. The model takes account of processes of binding/unbinding of transcription factors, formation/dissolution of transcription apparatus, and modification of histone code at each locus of genes in the network. These processes are hierarchically interrelated to each other forming the dynamical feedback loops. By simulating stochastic dynamics of this model, we show that the phenotypic heterogeneity of ESCs can be explained when the chromatin at the Nanog locus undergoes the large scale reorganization in formation/dissolution of transcription apparatus, which should have the timescale similar to the cell cycle period. With this slow transcriptional switching of Nanog, the simulated ESCs fluctuate among multiple transient states, which can trigger the differentiation into the lineage-specific cell states. From the simulated transitions among cell states, the epigenetic landscape underlying transitions is calculated. The slow Nanog switching gives rise to the wide basin of ESC states in the landscape. The bimodal Nanog distribution arising from the kinetic flow running through this ESC basin prevents transdifferentiation and promotes the definite decision of the cell fate. These results show that the distribution of timescales of the regulatory processes is decisively important to characterize the fluctuation of cells and their differentiation process. The analyses through the epigenetic landscape and the kinetic flow on the landscape should provide a guideline to engineer cell differentiation.
言語 en
内容記述タイプ Abstract
出版者
言語 en
出版者 PLOS
言語
言語 eng
資源タイプ
資源タイプresource http://purl.org/coar/resource_type/c_6501
タイプ journal article
出版タイプ
出版タイプ VoR
出版タイプResource http://purl.org/coar/version/c_970fb48d4fbd8a85
DOI
関連タイプ isVersionOf
識別子タイプ DOI
関連識別子 https://doi.org/10.1371/journal.pcbi.1003380
ISSN
収録物識別子タイプ PISSN
収録物識別子 1553-734X
書誌情報 en : PLOS Computational Biology

巻 9, 号 12, p. e1003380-e1003380, 発行日 2013-12
著者版フラグ
値 publisher
URI
識別子 http://dx.doi.org/10.1371/journal.pcbi.1003380
識別子タイプ DOI
URI
識別子 http://hdl.handle.net/2237/20624
識別子タイプ HDL
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