TY - JOUR
T1 - Cellular Resolution Maps of X Chromosome Inactivation
T2 - Implications for Neural Development, Function, and Disease
AU - Wu, Hao
AU - Luo, Junjie
AU - Yu, Huimin
AU - Rattner, Amir
AU - Mo, Alisa
AU - Wang, Yanshu
AU - Smallwood, Philip M.
AU - Erlanger, Bracha
AU - Wheelan, Sarah J.
AU - Nathans, Jeremy
N1 - Funding Information:
The authors thank Elizabeth Simpson for the gift of Hprt mutant ES cells, Dominic Ciavatta for the Hprt targeting vector, Dwight Bergles, Karl Deisseroth, Alex Kolodkin, and Se-Jin Lee for Cre lines, Terry Shelley for custom manufacturing support, the members of the Johns Hopkins Transgenic, Flow Cytometry, and NextGen Sequencing core facilities for blastocyst injection, FACS sorting, and RNA-seq library construction, John Williams for assistance with genotyping, and Rudolf Jaenisch, Lucas Hua, Barbara Migeon, and Max Tischfield for helpful discussions and/or comments on the manuscript. Supported by National Institutes of Health P30 CA006973 (S.J.W.), the Human Frontier Science Program (H.W.), the Howard Hughes Medical Institute, and the Brain Sciences Institute of the Johns Hopkins University.
PY - 2014/1/8
Y1 - 2014/1/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neuron.2013.10.051
DO - 10.1016/j.neuron.2013.10.051
M3 - Article
C2 - 24411735
AN - SCOPUS:84891818179
SN - 0896-6273
VL - 81
SP - 103
EP - 119
JO - Neuron
JF - Neuron
IS - 1
ER -