Lineage-specific dynamics of loss of X upregulation during inactive-X reactivation

Naik, HC and Chandel, D and Majumdar, S and Arava, M and Baro, R and BV, H and Hari, K and Ayyamperumal, P and Manhas, A and Jolly, MK and Gayen, S (2024) Lineage-specific dynamics of loss of X upregulation during inactive-X reactivation. In: Stem Cell Reports, 19 (11). pp. 1564-1582.

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Abstract

In mammals, X chromosome dosage is balanced between sexes through the silencing of one X chromosome in females. Recent single-cell RNA sequencing analysis demonstrated that the inactivation of the X chromosome is accompanied by the upregulation of the active X chromosome (Xa) during mouse embryogenesis. Here, we have investigated if the reactivation of inactive-X (Xi) leads to the loss of Xa upregulation in different cellular or developmental contexts. We find that while Xi reactivation and loss of Xa upregulation are tightly coupled in mouse embryonic epiblast and induced pluripotent stem cells, that is not the case in germ cells. Moreover, we demonstrate that partial reactivation of Xi in mouse extra-embryonic endoderm stem cells and human B cells does not result in the loss of Xa upregulation. Finally, we have established a mathematical model for the transcriptional coordination of two X chromosomes. Together, we conclude that the reactivation of Xi is not always synchronized with the loss of Xa upregulation. © 2024 The Author(s)

Item Type:	Journal Article
Publication:	Stem Cell Reports
Publisher:	Cell Press
Additional Information:	The copyright for this article belongs to the author.
Keywords:	guide RNA, allele; animal cell; animal experiment; animal tissue; Article; autosome; blastocyst; cell differentiation; cell reprogramming technique; controlled study; ectoderm; embryo; embryonic stem cell; female; gene expression; gene expression profiling; germ cell; induced pluripotent stem cell; male; MEF cell line; mouse; nonhuman; primordial germ cell; protein depletion; RNA sequencing; single cell RNA seq; upregulation; X chromosome; X chromosome inactivation
Department/Centre:	Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering Division of Physical & Mathematical Sciences > Mathematics
Date Deposited:	28 Nov 2024 05:56
Last Modified:	28 Nov 2024 05:56
URI:	http://eprints.iisc.ac.in/id/eprint/86891

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