RRC ID 70121
Author 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.
Title Early reactivation of clustered genes on the inactive X chromosome during somatic cell reprogramming.
Journal Stem Cell Reports
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.
Volume 17(1)
Pages 53-67
Published 2022-1-11
DOI 10.1016/j.stemcr.2021.11.008
PII S2213-6711(21)00589-0
PMID 34919813
PMC PMC8758948
MeSH Alleles Animals Biomarkers Cell Differentiation / genetics* Cellular Reprogramming / genetics* Cellular Reprogramming Techniques Fibroblasts Gene Expression Profiling High-Throughput Nucleotide Sequencing Histone Demethylases Mice Multigene Family* Real-Time Polymerase Chain Reaction Single-Cell Analysis Transcriptional Activation* Transcriptome X Chromosome Inactivation / genetics*
IF 6.032
Mice RBRC00208 RBRC02467