Variability of cross-tissue X-chromosome inactivation characterizes timing of human embryonic lineage specification events.
Variability of cross-tissue X-chromosome inactivation characterizes timing of human embryonic lineage specification events.
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DOI：
10.1016/j.devcel.2022.07.007
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发表时间：
2022-08-22
影响因子：
11.8
通讯作者：
Gillis, Jesse
中科院分区：
文献类型：
--
作者：
Werner, Jonathan M.;Ballouz, Sara;Hover, John;Gillis, Jesse
X染色体失活（XCI）是发生在哺乳动物胚胎发育过程中的一种随机的、永久的、发育早期的表观遗传事件。我们利用这些功能来研究人类发育过程中早期谱系特化事件的特征。我们首先评估X-失活的一致性，并建立一个强大的XCI逃逸基因集。通过分析组织和个体间XCI比率的方差，我们发现XCI在所有组织中是共享的，这表明XCI在胚层特化之前在外胚层（至少6-16个细胞）中完成。此外，我们利用组织特异性变异来表征组织谱系定型过程中存在的细胞数量，范围从肝脏和全血组织中的约20个细胞到脑组织中的80个细胞。通过研究成人组织中XCI比率的变异性，我们表征了人类XCI的胚胎特征和谱系规范，否则难以通过实验确定。Werner等人使用GTEx数据集对不同组织和个体的人类XCI比率的变异性进行建模，确定XCI比率在所有组织谱系中是一致的。这表明在成年群体中观察到的XCI变异性可以通过小细胞库中发生的随机胚胎事件的统计数据来解释。
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 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 variability of XCI ratios using adult tissue, we characterize embryonic features of human XCI and lineage specification otherwise difficult to ascertain experimentally. Werner et al. model variability in human XCI ratios across tissues and individuals using the GTEx dataset, determining XCI ratios are consistent across all tissue lineages. This suggests observed XCI variability in adult populations is explained by the statistics of a stochastic embryonic event occurring in a small cell pool.
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影响因子：
4
作者：
Bittel, D. C.;Theodoro, M. F.;Butler, M. G.
通讯作者：
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影响因子：
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作者：
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DOI：
10.1093/bioinformatics/btx346
发表时间：
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期刊：
Bioinformatics (Oxford, England)
影响因子：
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通讯作者：
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作者：
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作者：
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通讯作者：
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