First Author | Cai X | Year | 2011 |
Journal | PLoS One | Volume | 6 |
Issue | 12 | Pages | e28430 |
PubMed ID | 22145044 | Mgi Jnum | J:182271 |
Mgi Id | MGI:5315082 | Doi | 10.1371/journal.pone.0028430 |
Citation | Cai X, et al. (2011) Runx1 loss minimally impacts long-term hematopoietic stem cells. PLoS One 6(12):e28430 |
abstractText | RUNX1 encodes a DNA binding subunit of the core-binding transcription factors and is frequently mutated in acute leukemia, therapy-related leukemia, myelodysplastic syndrome, and chronic myelomonocytic leukemia. Mutations in RUNX1 are thought to confer upon hematopoietic stem cells (HSCs) a pre-leukemic state, but the fundamental properties of Runx1 deficient pre-leukemic HSCs are not well defined. Here we show that Runx1 deficiency decreases both apoptosis and proliferation, but only minimally impacts the frequency of long term repopulating HSCs (LT-HSCs). It has been variously reported that Runx1 loss increases LT-HSC numbers, decreases LT-HSC numbers, or causes age-related HSC exhaustion. We attempt to resolve these discrepancies by showing that Runx1 deficiency alters the expression of several key HSC markers, and that the number of functional LT-HSCs varies depending on the criteria used to score them. Finally, we identify genes and pathways, including the cell cycle and p53 pathways that are dysregulated in Runx1 deficient HSCs. |