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Related Concept Videos

Development of the Heart01:27

Development of the Heart

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The development of the human heart, a crucial organ, commences from the mesoderm on the 18th or 19th day after fertilization. This process initiates in the cardiogenic area, a group of mesodermal cells at the embryo's head end, which evolves into elongated strands known as cardiogenic cords. These cords undergo a transformation to form hollow-centered endocardial tubes.
As the embryo undergoes lateral folding, these paired tubes approach each other, merging into a single primitive heart...
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Generating Self-Assembling Human Heart Organoids Derived from Pluripotent Stem Cells
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Epigenomic and Transcriptomic Dynamics During Human Heart Organogenesis.

Jennifer VanOudenhove1, Tara N Yankee1,2, Andrea Wilderman1,2

  • 1Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, Farmington, CT (J.V., T.N.Y., A.W., J.C.).

Circulation Research
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Researchers identified novel heart enhancers and gene networks active during human heart development. These findings link genetic variations in regulatory sequences to congenital heart defects, aiding future genetic diagnoses.

Keywords:
developmental biologydiseaseepigenomicsgeneticsgenomics

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Area of Science:

  • Genomics and Developmental Biology
  • Cardiovascular Genetics

Background:

  • Congenital heart defects (CHDs) are common birth defects with a significant genetic basis, but the causes for many cases remain unknown.
  • Regulatory sequences, rather than gene mutations, are increasingly implicated in complex genetic diseases like CHDs.

Purpose of the Study:

  • To identify regulatory sequences and gene expression networks crucial for human heart development.
  • To investigate the enrichment of disease-relevant genes and genetic variations within these cardiac regulatory elements and networks.

Main Methods:

  • Characterized chromatin states (ChromHMM) and gene expression dynamics across 9 stages of human embryonic heart development.
  • Profiled 7 histone modifications and performed RNA-sequencing to identify enhancers and gene coexpression networks.
  • Compared cardiac regulatory maps with over 100 human tissues and cell types.

Main Results:

  • Identified 177,412 heart enhancers, including 12,395 novel strong enhancers.
  • Validated 92% of known heart enhancers, showing significant enrichment (7.5x) for functionally validated sites.
  • Found novel enhancers near cardiac-specific genes and enriched for variants associated with ECG traits and atrial fibrillation.

Conclusions:

  • Heart-specific enhancers target well-connected hub genes with cardiac expression, identifying potential candidates for CHDs.
  • Functional annotations of regulatory elements improve the interpretation of whole-genome sequencing data for CHD patients.