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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-03-0937.
Submitted March 26, 2002
Accepted June 24, 2002
Immortalization of yolk sac-derived precursor cells
Wen-Mei Yu, Teresa S Hawley, Robert G Hawley, and Cheng-Kui Qu*
Department of Hematopoiesis, Holland Laboratory, American Red Cross, Rockville, MD, USA
Department of Hematopoiesis, Holland Laboratory, American Red Cross, Rockville, MD, USA; Flow Cytometry Facility, Holland Laboratory, American Red Cross, Rockville, MD, USA
Department of Hematopoiesis, Holland Laboratory, American Red Cross, Rockville, MD, USA; Department of Anatomy and Cell Biology, George Washington University Medical Center, Washington, DC, USA
* Corresponding author; email: quc{at}usa.redcross.org.
Hematopoiesis initiates in the extraembryonic yolk sac. To isolate various types of precursor cells from this blood cell-forming tissue, yolk sac cells were immortalized by retroviral-mediated expression of the HOX11 homeobox-containing gene. Among the cell lines derived, some were able to spontaneously generate adherent stromal-like cells capable of taking up acetylated low-density lipoprotein, and they could be induced to form tube-like structures when cultured on Matrigel. Although these cell lines were negative for hematopoietic cell markers, they gave rise to hematopoietic colonies -- containing cells belonging to the monocytic, megakaryocytic, and definitive erythroid lineages -- when plated in methylcellulose medium supplemented with hematopoietic growth factors. Low amounts of Flk-1 mRNA could be detected in these cells, and they showed significant responsiveness to vascular endothelial growth factor, stem cell factor, basic fibroblast growth factor, and interleukin-6. They also expressed the transcription factors SCL, GATA2, GATA1, PU.1, and c-myb. These yolk sac-derived cell lines may represent a transitional stage of early hematopoietic development.
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