| First Author | Nemeth MJ | Year | 2006 |
| Journal | Proc Natl Acad Sci U S A | Volume | 103 |
| Issue | 37 | Pages | 13783-8 |
| PubMed ID | 16945912 | Mgi Jnum | J:113745 |
| Mgi Id | MGI:3687604 | Doi | 10.1073/pnas.0604006103 |
| Citation | Nemeth MJ, et al. (2006) Hmgb3 regulates the balance between hematopoietic stem cell self-renewal and differentiation. Proc Natl Acad Sci U S A 103(37):13783-8 |
| abstractText | Hmgb3 is an X-linked member of a family of sequence-independent chromatin-binding proteins that is preferentially expressed in hematopoietic stem cells (HSC). Hmgb3-deficient mice (Hmgb3(-/Y)) contain normal numbers of HSCs, capable of self-renewal and hematopoietic repopulation, but fewer common lymphoid (CLP) and common myeloid progenitors (CMP). In this study, we tested the hypothesis that Hmgb3(-/Y) HSCs are biased toward self-renewal at the expense of progenitor production. Wild-type and Hmgb3(-/Y) CLPs and CMPs proliferate and differentiate equally in vitro, indicating that CLP and CMP function normally in Hmgb3(-/Y) mice. Hmgb3(-/Y) HSCs exhibit constitutive activation of the canonical Wnt signaling pathway, which regulates stem cell self-renewal. Increased Wnt signaling in Hmgb3(-/Y) HSCs corresponds to increased expression of Dvl1, a positive regulator of the canonical Wnt pathway. To induce hematopoietic stress and a subsequent response from HSCs, we treated Hmgb3(-/Y) mice with 5-fluorouracil. Hmgb3(-/Y) mice exhibit a faster recovery of functional HSCs after administration of 5-fluorouracil compared with wild-type mice, which may be due to the increased Wnt signaling. Furthermore, the recovery of HSC number in Hmgb3(-/Y) mice occurs more rapidly than CLP and CMP recovery. From these data, we propose a model in which Hmgb3 is required for the proper balance between HSC self-renewal and differentiation. |
