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Related Concept Videos

Neural Regulation01:37

Neural Regulation

Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
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Spinal Cord: Information Processing

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Development of the Heart

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.
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Epigenetic Regulation of Cardiac Differentiation of Embryonic Stem Cells and Tissues
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Deep learning the dynamic regulatory sequence code of cardiac organoid differentiation.

Eyal Metzl-Raz1, Ryan Zhao2, Salil Deshpande3

  • 1Department of Genetics, Stanford University, Stanford, CA, USA.

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|November 24, 2025
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Researchers mapped gene regulatory programs in developing human heart organoids using single-cell multi-omics and deep learning. This revealed key rules for heart development and identified potential causes of congenital heart disease.

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Area of Science:

  • Developmental Biology
  • Genomics
  • Cardiovascular Research

Background:

  • Understanding human organogenesis, particularly heart development, is crucial for addressing congenital diseases.
  • Temporal gene regulatory programs are key to normal embryonic development.
  • Congenital heart defects often arise from disruptions in early developmental processes.

Purpose of the Study:

  • To define the temporal gene regulatory programs driving human cardiac organogenesis.
  • To uncover the regulatory syntax governing early heart development using advanced computational methods.
  • To link developmental gene regulation to the genetic basis of congenital heart disease.

Main Methods:

  • Generated a time-resolved, single-cell multi-omic atlas of human induced pluripotent stem cell-derived cardiac organoids.
  • Employed deep learning models to predict chromatin accessibility from DNA sequence.
  • Integrated multi-omic data (chromatin, transcriptional, genetic) to identify regulatory elements and disease variants.

Main Results:

  • Discovered cell-state-specific rules of cardiogenesis and context-dependent transcription factor activities (TEAD, HAND, TBX).
  • Identified distinct programs controlling cardiomyocyte lineage divergence (e.g., ventricular vs. pacemaker).
  • Validated the essential role of Myocardin (MYOCD) in ventricular cardiomyocyte specification through perturbation experiments.

Conclusions:

  • This study elucidates the complex gene regulatory networks underlying human heart development.
  • The findings highlight early developmental origins of congenital heart disease and identify specific regulatory mechanisms.
  • Provides a foundation for mechanistic understanding and therapeutic strategies for congenital heart conditions.