Journal
STEM CELLS
Volume 21, Issue 3, Pages 272-280Publisher
WILEY
DOI: 10.1634/stemcells.21-3-272
Keywords
embryonic stem cells; hemangioblast; thrombopoietin; c-Mpl
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Funding
- NATIONAL CANCER INSTITUTE [R01CA086991, R29CA076418] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK059279] Funding Source: NIH RePORTER
- NCI NIH HHS [CA86991, CA76418] Funding Source: Medline
- NIDDK NIH HHS [DK59279] Funding Source: Medline
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Vascular endothelial growth factor (VEGF) and stem cell factor (SCF) act as growth factors for the hemangioblast, an embryonic progenitor of the hematopoietic and endothelial lineages. Because thrombopoietin (TPO) and its receptor, c-Mp1, regulate primitive hematopoietic populations, including bone marrow hematopoietic stem cells, we investigated whether TPO acts on the hemangioblasts that derive from differentiation of embryonic stem cells in vitro. Reverse transcriptase polymerase chain reaction analysis detected expression of c-Mp1 beginning on day 3 of embryoid body differentiation when the hemangioblast first arises. In assays of the hemangioblast colony-forming cell (BL-CFC), TPO alone supported BL-CFC formation and nearly doubled the number of BL-CFC when added together with VEGF and SCF. When replated under the appropriate conditions, TPO-stimulated BL-CFC gave rise to secondary hematopoietic colonies, as well as endothelial cells, confirming their nature as hemangioblasts. Addition of a neutralizing anti-VEGF antibody did not block TPO enhancement of BL-CFC formation, suggesting that TPO acts independently of VEGF. These results establish that Mp1 signaling plays a role in the earliest stages of hematopoietic development and that TPO represents a third growth factor influencing hemangioblast formation.
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