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Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
Diversity in Cell Signaling Responses01:22

Diversity in Cell Signaling Responses

The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity. 
Graded and Abrupt Responses
Some signaling systems generate...

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Updated: Jun 25, 2026

Directed Differentiation of Hemogenic Endothelial Cells from Human Pluripotent Stem Cells
04:23

Directed Differentiation of Hemogenic Endothelial Cells from Human Pluripotent Stem Cells

Published on: March 31, 2021

Signaling hierarchy regulating human endothelial cell development.

Melissa A Kelly1, Karen K Hirschi

  • 1Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.

Arteriosclerosis, Thrombosis, and Vascular Biology
|February 14, 2009
PubMed
Summary
This summary is machine-generated.

Indian hedgehog (Ihh) signaling promotes human endothelial cell differentiation from pluripotent stem cells via bone morphogenetic protein (BMP) pathways, offering new therapeutic strategies for vascular regeneration.

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Area of Science:

  • Stem cell biology
  • Developmental biology
  • Vascular biology

Background:

  • Mammalian endothelial cell differentiation knowledge primarily stems from mouse models.
  • Human endothelial cell development mechanisms and signaling hierarchies remain largely uncharacterized.

Purpose of the Study:

  • To investigate the unique signaling pathways regulating human endothelial cell differentiation from human embryonic stem cells (hESCs).
  • To identify key signaling molecules that promote or inhibit human endothelial cell development.

Main Methods:

  • Utilized human embryonic stem cells (hESCs) cocultured on OP9 marrow stromal cells to generate endothelial cells.
  • Assessed the effects of fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), Indian hedgehog (Ihh), and bone morphogenetic protein (BMP) signaling pathways.
  • Employed neutralizing antibodies against BMP signaling components and hedgehog inhibitors (cyclopamine).

Main Results:

  • Fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) did not specifically influence human vasculogenesis initiation.
  • Exogenous Indian hedgehog (Ihh) significantly promoted endothelial cell differentiation, characterized by cobblestone morphology, endothelial gene/protein expression, lumen formation, and DiI-AcLDL uptake.
  • Inhibition of bone morphogenetic protein (BMP) signaling suppressed endothelial cell formation, while BMP4 addition rescued development in the presence of a hedgehog inhibitor.

Conclusions:

  • Indian hedgehog (Ihh) signaling promotes human endothelial cell differentiation from pluripotent hESCs through bone morphogenetic protein (BMP) signaling.
  • These findings provide novel insights for modulating human endothelial cell formation and vascular regeneration in clinical therapies.