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

被引：158

作者：

Wu, Hao ^{[1
,7
]}

Luo, Junjie ^{[2
]}

Yu, Huimin ^{[1
]}

Rattner, Amir ^{[1
]}

Mo, Alisa ^{[3
]}

Wang, Yanshu ^{[1
,7
]}

Smallwood, Philip M. ^{[1
,7
]}

Erlanger, Bracha ^{[4
]}

Wheelan, Sarah J. ^{[4
,6
]}

Nathans, Jeremy ^{[1
,3
,5
,7
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA

[6] Johns Hopkins Univ, Sch Med, Div Biostat & Bioinformat, Baltimore, MD 21205 USA

[7] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA

来源：

NEURON | 2014年 / 81卷 / 01期

基金：

美国国家卫生研究院;

关键词：

RETINAL VASCULAR DEVELOPMENT; NORRIE-DISEASE; COLOR-VISION; EXPRESSION; ORIGIN; TRANSGENE; DISPERSION; MUTATIONS; CHROMATIN; CARRIERS;

D O I：

10.1016/j.neuron.2013.10.051

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Female eutherian mammals use X chromosome inactivation (XCI) to epigenetically regulate gene expression from similar to 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.

引用

页码：103 / 119

页数：17

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