期刊
DEVELOPMENTAL CELL
卷 39, 期 4, 页码 480-490出版社
CELL PRESS
DOI: 10.1016/j.devcel.2016.10.001
关键词
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资金
- Howard Hughes Medical Institute Funding Source: Medline
- NHLBI NIH HHS [K08 HL125807, R01 HL084553, R01 HL080494, UM1 HL098179, T32 HL007208, UM1 HL098166, U01 HL098147, UM1 HL098147, U01 HL066582, U01 HL098179, U01 HL098166] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007753] Funding Source: Medline
- NIMH NIH HHS [R01 MH101528] Funding Source: Medline
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, spatiotemporal developmental programs, we performed single-cell RNA sequencing of >1,200 murine cells isolated at seven time points spanning embryonic day 9.5 (primordial heart tube) to postnatal day 21 (mature heart). Using unbiased transcriptional data, we classified cardiomyocytes, endothelial cells, and fibroblast-enriched cells, thus identifying markers for temporal and chamber-specific developmental programs. By harnessing these datasets, we defined developmental ages of human and mouse pluripotent stem-cell-derived cardiomyocytes and characterized lineage-specific maturation defects in hearts of mice with heterozygous mutations in Nkx2.5 that cause human heart malformations. This spatiotemporal transcriptome analysis of heart development reveals lineage-specific gene programs underlying normal cardiac development and congenital heart disease.
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