Hypoxia affects mesoderm and enhances hemangioblast specification during early development

Diana L. Ramírez-Bergeron, Anja Runge, Karen Cowden Dahl, Hans Joerg Fehling, Gordon Keller, M. Celeste Simon

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Hypoxia Inducible Factor (HIF), consisting of HIF1α and ARNT (HIF1β) subunits, activates multiple genes in response to oxygen (O2) deprivation. Arnt-1- mice exhibit substantial defects in blood cell and vessel development. We demonstrate that hypoxia accelerates the expression of Brachyury (a mesoderm-specific transcription factor), BMP4 (a mesoderm-promoting growth factor) and FLK1 (a marker of hemangioblasts, the bipotential progenitor of endothelial and hematopoietic cells) in differentiating ES cell cultures. Significantly, proliferation of embryonic hemangioblasts (BL-CFCs) is regulated by hypoxia, as Arnt+/+ ES cells generate increased numbers of FLK1+ cells, and BL-CFCs with accelerated kinetics in response to low O2. This response is HIF-dependent as Arnt-/- ES cells produce fewer FLK1+ cells and BL-CFCs, under both normoxic and hypoxic conditions. Interestingly, this defect is rescued when Arnt-/- ES cells are co-cultured with Arnt+/+ ES cells. Vegf+/-or Vegf-/- ES cells generate proper numbers of FLK1+ cells but fewer BL-CFCs, suggesting that additional factors regulated by HIF (other than VEGF) are involved in these early events. Thus, hypoxic responses are important for the establishment of various progenitor cells, including early mesoderm and its differentiation into hemangioblasts. Together these data suggest that ineffective responses to hypoxia in Arnt-/- embryos abrogate proper cardiovascular development during early embryogenesis, including the pathways controlling hemangioblast differentiation.

Original languageEnglish (US)
Pages (from-to)4623-4634
Number of pages12
JournalDevelopment (Cambridge)
Volume131
Issue number18
DOIs
StatePublished - Sep 2004
Externally publishedYes

Fingerprint

Hemangioblasts
Mesoderm
Vascular Endothelial Growth Factor A
Cell Count
Hematopoietic Stem Cells
Embryonic Development
Blood Vessels
Hypoxia
Cultured Cells
Blood Cells
Intercellular Signaling Peptides and Proteins
Transcription Factors
Stem Cells
Embryonic Structures
Cell Culture Techniques
Oxygen

Keywords

  • ARNT
  • Hemangioblast
  • HIF
  • Hypoxia
  • Mesoderm

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Ramírez-Bergeron, D. L., Runge, A., Cowden Dahl, K., Fehling, H. J., Keller, G., & Simon, M. C. (2004). Hypoxia affects mesoderm and enhances hemangioblast specification during early development. Development (Cambridge), 131(18), 4623-4634. https://doi.org/10.1242/dev.01310

Hypoxia affects mesoderm and enhances hemangioblast specification during early development. / Ramírez-Bergeron, Diana L.; Runge, Anja; Cowden Dahl, Karen; Fehling, Hans Joerg; Keller, Gordon; Simon, M. Celeste.

In: Development (Cambridge), Vol. 131, No. 18, 09.2004, p. 4623-4634.

Research output: Contribution to journalArticle

Ramírez-Bergeron, DL, Runge, A, Cowden Dahl, K, Fehling, HJ, Keller, G & Simon, MC 2004, 'Hypoxia affects mesoderm and enhances hemangioblast specification during early development', Development (Cambridge), vol. 131, no. 18, pp. 4623-4634. https://doi.org/10.1242/dev.01310
Ramírez-Bergeron DL, Runge A, Cowden Dahl K, Fehling HJ, Keller G, Simon MC. Hypoxia affects mesoderm and enhances hemangioblast specification during early development. Development (Cambridge). 2004 Sep;131(18):4623-4634. https://doi.org/10.1242/dev.01310
Ramírez-Bergeron, Diana L. ; Runge, Anja ; Cowden Dahl, Karen ; Fehling, Hans Joerg ; Keller, Gordon ; Simon, M. Celeste. / Hypoxia affects mesoderm and enhances hemangioblast specification during early development. In: Development (Cambridge). 2004 ; Vol. 131, No. 18. pp. 4623-4634.
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