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Single-Cell Resolution of Temporal Gene Expression during Heart Development.
- 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.)
- Subjects :
- Animals
Cell Differentiation genetics
Cell Lineage genetics
Endothelial Cells cytology
Endothelial Cells metabolism
Fibroblasts cytology
Fibroblasts metabolism
Gene Expression Profiling
Haploinsufficiency genetics
Heart Atria cytology
Heart Ventricles cytology
Homeobox Protein Nkx-2.5 metabolism
Humans
Mice
Myocytes, Cardiac cytology
Myocytes, Cardiac metabolism
Sequence Analysis, RNA
Time Factors
Transcriptome genetics
Gene Expression Regulation, Developmental
Heart embryology
Single-Cell Analysis methods
Subjects
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