Single-Cell Resolution of Temporal Gene Expression during Heart Development.

Single-Cell Resolution of Temporal Gene Expression during Heart Development.
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DOI:
10.1016/j.devcel.2016.10.001
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发表时间:
2016-11-21
期刊:
影响因子:
11.8
通讯作者:
Seidman, Christine E.
Seidman, Christine E.
中科院分区:
生物学1区
文献类型:
--
作者:
DeLaughter, Daniel M.;Bick, Alexander G.;Wakimoto, Hiroko;McKean, David;Gorham, Joshua M.;Kathiriya, Irian S.;Hinson, John T.;Homsy, Jason;Gray, Jesse;Pu, William;Bruneau, Benoit G.;Seidman, J. G.;Seidman, Christine E.

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Activation of complex molecular programs in specific cell lineages governs mammalian heart development, from a primordial linear tube to a four-chamber organ. To characterize lineage-specific, temporal-spatial developmental programs, we performed single-cell RNA sequencing of >1200 murine cells isolated at seven time points spanning E9.5 (primordial heart tube) to P21 (mature heart). Using unbiased transcriptional data we classified cardiomyocytes (CM), endothelial cells (EC), and fibroblast-enriched cells, thus identifying markers for temporal and chamber-specific developmental programs. Harnessing these datasets, we defined developmental ages of human and mouse pluripotent stem cell-derived CMs and characterized lineage-specific maturation defects in hearts of mice with heterozygous mutations in Nkx2.5 that cause human heart malformations. This spatial-temporal transcriptome analysis of heart development reveals lineage-specific gene programs underlying normal cardiac development and congenital heart disease.
雏鸡和小鼠心内膜垫的空间转录曲线在体外鉴定了内膜EMT的新调节剂。
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