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

Jonathan M. Werner, View ORCID ProfileSara Ballouz, John Hover, View ORCID ProfileJesse Gillis
doi: https://doi.org/10.1101/2021.09.13.460075
Jonathan M. Werner
1The Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724, USA
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Sara Ballouz
1The Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724, USA
2Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia
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  • ORCID record for Sara Ballouz
John Hover
1The Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724, USA
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Jesse Gillis
1The Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 11724, USA
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  • ORCID record for Jesse Gillis
  • For correspondence: jgillis@cshl.edu
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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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 14, 2021.
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Cross-tissue analysis of allelic X-chromosome inactivation ratios resolves features of human development
Jonathan M. Werner, Sara Ballouz, John Hover, Jesse Gillis
bioRxiv 2021.09.13.460075; doi: https://doi.org/10.1101/2021.09.13.460075
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Cross-tissue analysis of allelic X-chromosome inactivation ratios resolves features of human development
Jonathan M. Werner, Sara Ballouz, John Hover, Jesse Gillis
bioRxiv 2021.09.13.460075; doi: https://doi.org/10.1101/2021.09.13.460075

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