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The Cdx‐Hox Pathway in Hematopoietic Stem Cell Formation from Embryonic Stem Cells
Author(s) -
LENGERKE CLAUDIA,
McKINNEYFREEMAN SHAN,
NAVEIRAS OLAIA,
YATES FRANK,
WANG YUAN,
BANSAL DIMPLE,
DALEY GEORGE Q.
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1392.006
Subject(s) - hox gene , biology , embryonic stem cell , stem cell , hemangioblast , microbiology and biotechnology , zebrafish , yolk sac , haematopoiesis , homeobox , progenitor cell , adult stem cell , cellular differentiation , hematopoietic stem cell , genetics , transcription factor , gene , embryo
Embryonic stem cells (ESCs) differentiated in vitro will yield a multitude of hematopoietic derivatives, yet progenitors displaying true stem cell activity remain difficult to obtain. Possible causes are a biased differentiation to primitive yolk sac‐type hematopoiesis, and a variety of developmental or functional deficiencies. Recent studies in the zebrafish have identified the caudal homeobox transcription factors (cdx1/4) and posterior hox genes ( hoxa9a , hoxb7a ) as key regulators for blood formation during embryonic development. Activation of Cdx and Hox genes during the in vitro differentiation of mouse ESCs followed by co‐culture on supportive stromal cells generates ESC‐derived hematopoietic stem cells (HSCs) capable of multilineage repopulation of lethally irradiated adult mice. We show here that brief pulses of ectopic Cdx4 or HoxB4 expression are sufficient to enhance hematopoiesis during ESC differentiation, presumably by acting as developmental switches to activate posterior Hox genes. Insights into the role of the Cdx‐Hox gene pathway during embryonic hematopoietic development in the zebrafish have allowed us to improve the derivation of repopulating HSCs from murine ESCs.