Variability of cross-tissue X-chromosome inactivation characterizes timing of human embryonic lineage specification events

Werner, Jonathan M, Ballouz, Sara, Hover, John, Gillis, Jesse (July 2022) Variability of cross-tissue X-chromosome inactivation characterizes timing of human embryonic lineage specification events. Developmental Cell, 57 (16). S1534-5807(22)00496. ISSN 1534-5807

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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 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 shared across all tissues, suggesting that XCI is completed in the epiblast (in at least 6-16 cells) prior to specification of the germ layers. Additionally, we exploit tissue-specific variability to characterize the number of cells present during tissue-lineage commitment, ranging from approximately 20 cells in liver and whole blood tissues to 80 cells in brain tissues. By investigating the variability of XCI ratios using adult tissue, we characterize embryonic features of human XCI and lineage specification that are otherwise difficult to ascertain experimentally.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics organism description > animal 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 > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function organism description > animal > developmental stage organism description > animal > developmental stage > embryo organism description > animal > mammal
CSHL Authors:	Werner, Jonathan Ballouz, Sara Hover, John Gillis, Jesse
Communities:	CSHL labs > Gillis Lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	31 July 2022
Date Deposited:	23 Aug 2022 01:48
Last Modified:	17 Jan 2024 19:11
PMCID:	PMC9398941
URI:	https://repository.cshl.edu/id/eprint/40697

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