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Basic fibroblast growth factor positively regulates hematopoietic development
P Faloon1, E Arentson, A Kazarov
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Summary
Newly found BLast Colony Forming Cells (BL-CFCs) are key to understanding hematopoietic commitment. Research shows fibroblast growth factor receptor-1 (FGFR1) signaling is vital for hemangioblast proliferation and development.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Hematopoiesis
Background:
- BLAST Colony Forming Cells (BL-CFCs) derived from embryonic stem (ES) cells are the hemangioblast, a common progenitor for hematopoietic and endothelial cells.
- Studying BL-CFCs offers a unique window into the early events of hematopoietic commitment.
Purpose of the Study:
- To quantitatively assess the impact of mesoderm-inducing factors on hematopoietic lineage development using BL-CFC assays and Flk1(+) cell analysis.
- To elucidate the molecular events governing hemangioblast development by analyzing ES cell lines with targeted mutations in FGFR1 and SCL.
Main Methods:
- Utilized BL-CFC assays and fluorescent activated cell sorter (FACS) analysis for Flk1(+) cells.
- Investigated ES cell lines with targeted mutations in fibroblast growth factor receptor-1 (FGFR1) and the transcription factor SCL.
Main Results:
- BL-CFCs express the receptor tyrosine kinase Flk1.
- Fibroblast growth factor (FGF) signaling, particularly through FGFR1, is crucial for hemangioblast proliferation.
- Cells co-expressing Flk1 and SCL are proposed to represent the hemangioblast population.
Conclusions:
- Basic fibroblast growth factor (bFGF)-mediated signaling plays a critical role in hemangioblast proliferation.
- The combined expression of Flk1 and SCL may define the hemangioblast, providing a molecular marker for this progenitor cell population.