| First Author | Lieu YK | Year | 2009 |
| Journal | Proc Natl Acad Sci U S A | Volume | 106 |
| Issue | 51 | Pages | 21689-94 |
| PubMed ID | 19955420 | Mgi Jnum | J:155521 |
| Mgi Id | MGI:4414682 | Doi | 10.1073/pnas.0907623106 |
| Citation | Lieu YK, et al. (2009) Conditional c-myb knockout in adult hematopoietic stem cells leads to loss of self-renewal due to impaired proliferation and accelerated differentiation. Proc Natl Acad Sci U S A 106(51):21689-94 |
| abstractText | Hematopoietic stem cells (HSCs) have a unique capacity to undergo self-renewal and multi-lineage differentiation to provide a lifetime supply of mature blood cells. By using conditional knockout technology, we disrupted the c-myb proto-oncogene specifically in adult bone marrow (BM) to demonstrate that this transcription factor is a regulator of self-renewal and multi-lineage differentiation of adult HSCs. Targeted disruption of the c-myb gene resulted in a critical depletion of the HSC pool. In addition, BM hematopoiesis in adult mice was impaired, resulting in profound reductions of various hematopoietic lineages including neutrophilic, monocytic, B lymphoid, erythroid, and, unexpectedly, megakaryocytic cells. Serial BM transplantation into lethally irradiated recipient mice indicated an essential role for c-myb in the self-renewal process. Furthermore, in vitro functional assays demonstrated that deletion of the c-myb gene leads to a slightly reduced proliferative capacity and an aberrant and accelerated differentiation of HSCs. In addition to long-term HSCs, functional studies also show that c-myb plays a critical role in short-term HSCs and multi-potential progenitors. Collectively, our data indicate a critical role for c-myb in adult BM hematopoiesis and in self-renewal and multi-lineage differentiation of adult HSCs. |
