Cross-tissue analysis of allelic X-chromosome inactivation ratios resolves features of human development

Werner, Jonathan, Ballouz, Sara, Hover, John, Gillis, Jesse (September 2021) Cross-tissue analysis of allelic X-chromosome inactivation ratios resolves features of human development. BioRxiv. (Unpublished)

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Abstract

X-chromosome inactivation (XCI) is a random, permanent, and developmentally early epigenetic event that occurs during mammalian embryogenesis. We harness these features of XCI to investigate characteristics of early lineage specification events during human development. We initially assess the consistency of X-inactivation and establish a robust set of XCI-escape genes. By analyzing variance in XCI ratios across tissues and individuals, we find that XCI is completed prior to tissue specification and at a time when 6-16 cells are fated for all tissue lineages. Additionally, we exploit tissue specific variability to characterize the number of cells present at the time of each tissue’s lineage commitment, ranging from approximately 20 cells in liver and whole blood tissues to 80 cells in brain tissues. By investigating variance of XCI ratios using adult tissue, we resolve key features of human development otherwise difficult to ascertain experimentally and develop scalable methods easily applicable to future data.

Item Type:	Paper
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosome bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function > chromosome bioinformatics > computational biology organism description > animal > mammal > primates > hominids > human
CSHL Authors:	Werner, Jonathan Ballouz, Sara Gillis, Jesse Hover, John
Communities:	CSHL labs > Gillis Lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	14 September 2021
Date Deposited:	23 Sep 2021 15:25
Last Modified:	23 Sep 2021 15:25
URI:	https://repository.cshl.edu/id/eprint/40362

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