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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...
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The development of all multicellular organisms starts with the fusion of haploid cells called sperm and egg to form a diploid zygote. A zygote is a totipotent cell that can develop into a complete organism. The zygote undergoes cell division or cleavage to form an 8-cell mass. Until this stage, the cells are spherical, loosely attached, and remain totipotent. Totipotent cells are capable of developing both the embryonic and the extraembryonic tissues. However, as they continue to divide, they...
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Embryonic Stem Cells

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Embryonic Stem Cells

Embryonic stem (ES) cells were first discovered in mice in 1981 by Martin Evans. In 1998, James Thomson identified a method to isolate embryonic stem cells from humans. Human embryonic stem cells (hESCs) are obtained from 3-5 day old embryos that remain unused after an in vitro fertilization procedure.
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In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing
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Targeted Vezf1-null mutation impairs vascular structure formation during embryonic stem cell differentiation.

Zhongmin Zou1, Pauline A Ocaya, Huiqin Sun

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|May 1, 2010
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Vezf1 is crucial for vascular development, regulating endothelial cell differentiation and extracellular matrix formation. Its absence impairs vascular network formation and affects hematopoietic lineages.

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Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Stem Cell Biology

Background:

  • Vezf1 (VEZF1) is an early zinc finger transcription factor essential for vascular development.
  • Vezf1 function is dose-dependent and plays a role in endothelial cell differentiation and maturation.

Purpose of the Study:

  • Investigate the role of Vezf1 in endothelial cell differentiation and maturation.
  • Utilize in vitro embryoid body and in vivo teratocarcinoma models with mutant Vezf1 embryonic stem (ES) cells.

Main Methods:

  • Studied mutant Vezf1 ES cells in embryoid body differentiation models.
  • Analyzed teratocarcinoma formation and differentiation in vivo.
  • Performed histological and immunohistochemical examinations.

Main Results:

  • Vezf1-/- ES cell embryoid bodies showed vascular network and sprouting defects.
  • Loss of Vezf1 led to reduced retinol/vitamin A signaling and aberrant extracellular matrix (ECM) formation.
  • Vezf1 deficiency also caused defects in hematopoietic cell differentiation and altered ECM deposition in teratocarcinomas.

Conclusions:

  • Vezf1 is involved in early vascular differentiation.
  • Vezf1 regulates endothelial cell differentiation, proliferation, and ECM distribution.
  • The retinol pathway mediates Vezf1 function in vascular development.