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

Research output: Contribution to journalArticlepeer-review


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 languageEnglish
Pages (from-to)53-67
Number of pages15
JournalStem Cell Reports
Issue number1
Publication statusPublished - 11-01-2022

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology


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