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

Authors :
DeLaughter DM
Bick AG
Wakimoto H
McKean D
Gorham JM
Kathiriya IS
Hinson JT
Homsy J
Gray J
Pu W
Bruneau BG
Seidman JG
Seidman CE
Source :
Developmental cell [Dev Cell] 2016 Nov 21; Vol. 39 (4), pp. 480-490. Date of Electronic Publication: 2016 Nov 10.
Publication Year :
2016

Abstract

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.<br /> (Copyright © 2016 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1878-1551
Volume :
39
Issue :
4
Database :
MEDLINE
Journal :
Developmental cell
Publication Type :
Academic Journal
Accession number :
27840107
Full Text :
https://doi.org/10.1016/j.devcel.2016.10.001