Cellular Resolution Maps of X Chromosome Inactivation: Implications for Neural Development, Function, and Disease

Hao Wu, Junjie Luo, Huimin Yu, Amir Rattner, Alisa Mo, Yanshu Wang, Philip M. Smallwood, Bracha Erlanger, Sarah J. Wheelan, Jeremy Nathans

Research output: Contribution to journalArticlepeer-review

Abstract

Female eutherian mammals use X chromosome inactivation (XCI) to epigenetically regulate gene expression from ~4% of the genome. To quantitatively map the topography of XCI for defined cell types at single cell resolution, we have generated female mice that carry X-linked, Cre-activated, and nuclear-localized fluorescent reporters-GFP on one X chromosome and tdTomato on the other. Using these reporters in combination with different Cre drivers, we have defined the topographies of XCI mosaicism for multiple CNS cell types and of retinal vascular dysfunction in a model of Norrie disease. Depending on cell type, fluctuations in the XCI mosaic are observed over a wide range of spatial scales, from neighboring cells to left versus right sides of the body. These data imply a major role for XCI in generating female-specific,genetically directed, stochastic diversity in eutherian mammals on spatial scales that would be predicted to affect CNS function within and between individuals.

Original languageEnglish (US)
Pages (from-to)103-119
Number of pages17
JournalNeuron
Volume81
Issue number1
DOIs
StatePublished - Jan 8 2014

ASJC Scopus subject areas

  • Neuroscience(all)

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