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

Daniel M DeLaughter1, Alexander G Bick1, Hiroko Wakimoto1

  • 1Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

Developmental Cell
|November 15, 2016
PubMed
Summary

This study maps heart development using single-cell RNA sequencing, revealing key gene programs for cardiac cell lineages. These findings illuminate normal heart formation and congenital heart disease mechanisms.

Keywords:
ECMNkx2.5RNA-seqatriacardiogenesiscardiomyocyte maturationheartsingle cellventricle

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Area of Science:

  • Developmental Biology
  • Cardiovascular Research
  • Genomics

Background:

  • Mammalian heart development involves complex molecular programs in specific cell lineages.
  • Understanding lineage-specific, spatiotemporal developmental programs is crucial for studying congenital heart disease.

Purpose of the Study:

  • To characterize lineage-specific, spatiotemporal developmental programs during mammalian heart development.
  • To identify markers for temporal and chamber-specific cardiac developmental programs.
  • To define developmental ages of stem-cell-derived cardiomyocytes and analyze maturation defects in congenital heart disease models.

Main Methods:

  • Performed single-cell RNA sequencing on over 1,200 murine cells across seven developmental time points (embryonic day 9.5 to postnatal day 21).
  • Utilized unbiased transcriptional data to classify cardiomyocytes, endothelial cells, and fibroblast-enriched cells.
  • Analyzed lineage-specific maturation defects in Nkx2.5 heterozygous mutant mice.

Main Results:

  • Identified key markers for temporal and chamber-specific developmental programs in cardiac cell lineages.
  • Defined developmental ages for human and mouse pluripotent stem-cell-derived cardiomyocytes.
  • Characterized lineage-specific maturation defects in a mouse model of congenital heart disease caused by Nkx2.5 mutations.

Conclusions:

  • Spatiotemporal transcriptome analysis provides a comprehensive map of normal cardiac development.
  • Revealed lineage-specific gene programs critical for normal heart formation.
  • Offers insights into the molecular basis of congenital heart disease and potential therapeutic targets.