Early reactivation of clustered genes on the inactive X chromosome during somatic cell reprogramming

Shiho Aizawa; Ken Nishimura; Gonzalo Seminario Mondejar; Arun Kumar; Phuong Linh Bui; Yen Thi Hai Tran; Akihiro Kuno; Masafumi Muratani; Shin Kobayashi; Tsukasa Nabekura; Akira Shibuya; Eiji Sugihara; Taka Aki Sato; Aya Fukuda; Yohei Hayashi; Koji Hisatake

doi:10.1016/j.stemcr.2021.11.008

Early reactivation of clustered genes on the inactive X chromosome during somatic cell reprogramming

Shiho Aizawa, Ken Nishimura, Gonzalo Seminario Mondejar, Arun Kumar, Phuong Linh Bui, Yen Thi Hai Tran, Akihiro Kuno, Masafumi Muratani, Shin Kobayashi, Tsukasa Nabekura, Akira Shibuya, Eiji Sugihara, Taka Aki Sato, Aya Fukuda, Yohei Hayashi, Koji Hisatake

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Abstract

Reprogramming of murine female somatic cells to induced pluripotent stem cells (iPSCs) is accompanied by X chromosome reactivation (XCR), by which the inactive X chromosome (Xi) in female somatic cells becomes reactivated. However, how Xi initiates reactivation during reprogramming remains poorly defined. Here, we used a Sendai virus-based reprogramming system to generate partially reprogrammed iPSCs that appear to be undergoing the initial phase of XCR. Allele-specific RNA-seq of these iPSCs revealed that XCR initiates at a subset of genes clustered near the centromere region. The initial phase of XCR occurs when the cells transit through mesenchymal-epithelial transition (MET) before complete shutoff of Xist expression. Moreover, regulatory regions of these genes display dynamic changes in lysine-demethylase 1a (KDM1A) occupancy. Our results identified clustered genes on the Xi that show reactivation in the initial phase of XCR during reprogramming and suggest a possible role for histone demethylation in this process.

Original language	English
Pages (from-to)	53-67
Number of pages	15
Journal	Stem Cell Reports
Volume	17
Issue number	1
DOIs	https://doi.org/10.1016/j.stemcr.2021.11.008
Publication status	Published - 11-01-2022

All Science Journal Classification (ASJC) codes

Biochemistry
Genetics
Developmental Biology
Cell Biology

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Aizawa, S., Nishimura, K., Mondejar, G. S., Kumar, A., Bui, P. L., Tran, Y. T. H., Kuno, A., Muratani, M., Kobayashi, S., Nabekura, T., Shibuya, A., Sugihara, E., Sato, T. A., Fukuda, A., Hayashi, Y., & Hisatake, K. (2022). Early reactivation of clustered genes on the inactive X chromosome during somatic cell reprogramming. Stem Cell Reports, 17(1), 53-67. https://doi.org/10.1016/j.stemcr.2021.11.008

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title = "Early reactivation of clustered genes on the inactive X chromosome during somatic cell reprogramming",

abstract = "Reprogramming of murine female somatic cells to induced pluripotent stem cells (iPSCs) is accompanied by X chromosome reactivation (XCR), by which the inactive X chromosome (Xi) in female somatic cells becomes reactivated. However, how Xi initiates reactivation during reprogramming remains poorly defined. Here, we used a Sendai virus-based reprogramming system to generate partially reprogrammed iPSCs that appear to be undergoing the initial phase of XCR. Allele-specific RNA-seq of these iPSCs revealed that XCR initiates at a subset of genes clustered near the centromere region. The initial phase of XCR occurs when the cells transit through mesenchymal-epithelial transition (MET) before complete shutoff of Xist expression. Moreover, regulatory regions of these genes display dynamic changes in lysine-demethylase 1a (KDM1A) occupancy. Our results identified clustered genes on the Xi that show reactivation in the initial phase of XCR during reprogramming and suggest a possible role for histone demethylation in this process.",

author = "Shiho Aizawa and Ken Nishimura and Mondejar, {Gonzalo Seminario} and Arun Kumar and Bui, {Phuong Linh} and Tran, {Yen Thi Hai} and Akihiro Kuno and Masafumi Muratani and Shin Kobayashi and Tsukasa Nabekura and Akira Shibuya and Eiji Sugihara and Sato, {Taka Aki} and Aya Fukuda and Yohei Hayashi and Koji Hisatake",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s)",

year = "2022",

month = jan,

day = "11",

doi = "10.1016/j.stemcr.2021.11.008",

language = "English",

volume = "17",

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journal = "Stem Cell Reports",

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Aizawa, S, Nishimura, K, Mondejar, GS, Kumar, A, Bui, PL, Tran, YTH, Kuno, A, Muratani, M, Kobayashi, S, Nabekura, T, Shibuya, A, Sugihara, E, Sato, TA, Fukuda, A, Hayashi, Y & Hisatake, K 2022, 'Early reactivation of clustered genes on the inactive X chromosome during somatic cell reprogramming', Stem Cell Reports, vol. 17, no. 1, pp. 53-67. https://doi.org/10.1016/j.stemcr.2021.11.008

TY - JOUR

T1 - Early reactivation of clustered genes on the inactive X chromosome during somatic cell reprogramming

AU - Aizawa, Shiho

AU - Nishimura, Ken

AU - Mondejar, Gonzalo Seminario

AU - Kumar, Arun

AU - Bui, Phuong Linh

AU - Tran, Yen Thi Hai

AU - Kuno, Akihiro

AU - Muratani, Masafumi

AU - Kobayashi, Shin

AU - Nabekura, Tsukasa

AU - Shibuya, Akira

AU - Sugihara, Eiji

AU - Sato, Taka Aki

AU - Fukuda, Aya

AU - Hayashi, Yohei

AU - Hisatake, Koji

PY - 2022/1/11

Y1 - 2022/1/11

N2 - Reprogramming of murine female somatic cells to induced pluripotent stem cells (iPSCs) is accompanied by X chromosome reactivation (XCR), by which the inactive X chromosome (Xi) in female somatic cells becomes reactivated. However, how Xi initiates reactivation during reprogramming remains poorly defined. Here, we used a Sendai virus-based reprogramming system to generate partially reprogrammed iPSCs that appear to be undergoing the initial phase of XCR. Allele-specific RNA-seq of these iPSCs revealed that XCR initiates at a subset of genes clustered near the centromere region. The initial phase of XCR occurs when the cells transit through mesenchymal-epithelial transition (MET) before complete shutoff of Xist expression. Moreover, regulatory regions of these genes display dynamic changes in lysine-demethylase 1a (KDM1A) occupancy. Our results identified clustered genes on the Xi that show reactivation in the initial phase of XCR during reprogramming and suggest a possible role for histone demethylation in this process.

AB - Reprogramming of murine female somatic cells to induced pluripotent stem cells (iPSCs) is accompanied by X chromosome reactivation (XCR), by which the inactive X chromosome (Xi) in female somatic cells becomes reactivated. However, how Xi initiates reactivation during reprogramming remains poorly defined. Here, we used a Sendai virus-based reprogramming system to generate partially reprogrammed iPSCs that appear to be undergoing the initial phase of XCR. Allele-specific RNA-seq of these iPSCs revealed that XCR initiates at a subset of genes clustered near the centromere region. The initial phase of XCR occurs when the cells transit through mesenchymal-epithelial transition (MET) before complete shutoff of Xist expression. Moreover, regulatory regions of these genes display dynamic changes in lysine-demethylase 1a (KDM1A) occupancy. Our results identified clustered genes on the Xi that show reactivation in the initial phase of XCR during reprogramming and suggest a possible role for histone demethylation in this process.

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M3 - Article

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SN - 2213-6711

VL - 17

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EP - 67

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 1

ER -

Early reactivation of clustered genes on the inactive X chromosome during somatic cell reprogramming

Abstract

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