The homeobox gene Hhex regulates the earliest stages of definitive hematopoiesis.
The development and emergence of the hematopoietic stem cell involves a series of tightly regulated molecular events that are not well characterized. The hematopoietically expressed homeobox (Hhex) gene, a member of the homeobox gene family, is an essential regulator of embryogenesis and hematopoietic progenitor development. To investigate the role of Hhex in hematopoiesis we adapted a murine embryonic stem (ES) cell coculture system, in which ES cells can differentiate into CD41(+) and CD45(+) hematopoietic progenitors in vitro. Our results show that in addition to delayed hemangioblast development, Hhex(-/-) ES-derived progeny accumulate as CD41(+) and CD41(+)c-kit(+) cells, or the earliest definitive hematopoietic progenitors. In addition, Hhex(-/-) ES-derived progeny display a significantly reduced ability to develop into mature CD45(+) hematopoietic cells. The observed reduction in hematopoietic maturation was accompanied by reduced proliferation, because Hhex(-/-) CD41(+)CD45(-)c-kit(+) hematopoietic progenitors accumulated in the G(2) phase of the cell cycle. Thus, Hhex is a critical regulator of hematopoietic development and is necessary for the maturation and proliferation of the earliest definitive hematopoietic progenitors.
Paz
Helicia
H
Molecular Biology Interdepartmental Program, College of Letters and Science, University of California, Los Angeles, USA.
Lynch
Maureen R
MR
Bogue
Clifford W
CW
Gasson
Judith C
JC
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006410:Hematopoiesis; D018398:Homeodomain Proteins / Q000235:genetics*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*
C513080:Hhex protein, mouse; D018398:Homeodomain Proteins; D040201:Platelet Membrane Glycoprotein IIb; D012333:RNA, Messenger; D014157:Transcription Factors; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse
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