Hmgb3 deficiency deregulates proliferation and differentiation of common lymphoid and myeloid progenitors.
Hmgb3 is an X-linked member of a family of chromatin-binding proteins that is expressed in primitive hematopoietic cells capable of long-term hematopoietic repopulation. To examine the role of Hmgb3 in adult hematopoiesis, we generated Hmgb3-deficient (Hmgb3(-/Y)) mice, which are viable but erythrocythemic. Hmgb3(-/Y) mice contain normal numbers of hematopoietic stem cells (HSCs), which generate fewer than normal numbers of common lymphoid progenitors (CLPs) and common myeloid progenitors (CMPs) and greater than normal numbers of more mature progenitors. Although fewer Hmgb3(-/Y) primitive progenitor cells are in the G2/M cell cycle phase, bromodeoxyuridine (BrdU) incorporation demonstrated enhanced proliferation compared with their wild-type counterparts. Hmgb3(-/Y) HSCs have increased levels of Gata-2 and c-myb mRNA. We propose that Hmgb3 deficiency leads to a failure of HSCs to expand into normal numbers of CLPs and CMPs. This defect is compensated for by the ability of Hmgb3(-/Y) progenitors to expand rapidly and differentiate into normal numbers of hematopoietic cells.
Nemeth
Michael J
MJ
Hematopoiesis Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, MD 20892-4442, USA
Cline
Amanda P
AP
Anderson
Stacie M
SM
Garrett-Beal
Lisa J
LJ
Bodine
David M
DM
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics; D050989:GATA2 Transcription Factor; D015870:Gene Expression; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D025765:HMGB3 Protein / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000166:cytology; D023461:Myeloid Progenitor Cells / Q000166:cytology* / Q000502:physiology*; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics
D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; C494712:Gata2 protein, mouse; D025765:HMGB3 Protein; D020598:Proto-Oncogene Proteins c-myb; D014157:Transcription Factors; D016179:Granulocyte Colony-Stimulating Factor