| First Author | Holmfeldt P | Year | 2013 |
| Journal | Blood | Volume | 122 |
| Issue | 17 | Pages | 2987-96 |
| PubMed ID | 24041575 | Mgi Jnum | J:318674 |
| Mgi Id | MGI:6858791 | Doi | 10.1182/blood-2013-04-493973 |
| Citation | Holmfeldt P, et al. (2013) Nfix is a novel regulator of murine hematopoietic stem and progenitor cell survival. Blood 122(17):2987-96 |
| abstractText | Hematopoietic stem cells are both necessary and sufficient to sustain the complete blood system of vertebrates. Here we show that Nfix, a member of the nuclear factor I (Nfi) family of transcription factors, is highly expressed by hematopoietic stem and progenitor cells (HSPCs) of murine adult bone marrow. Although short hairpin RNA-mediated knockdown of Nfix expression in Lineage(-)Sca-1(+)c-Kit(+) HSPCs had no effect on in vitro cell growth or viability, Nfix-depleted HSPCs displayed a significant loss of colony-forming potential, as well as short- and long-term in vivo hematopoietic repopulating activity. Analysis of recipient mice at 4 to 20 days posttransplant revealed that Nfix-depleted HSPCs are established in the bone marrow, but fail to persist due to increased apoptotic cell death. Gene expression profiling of Nfix-depleted HSPCs reveals that loss of Nfix expression in HSPCs is concomitant with a decrease in the expression of multiple genes known to be important for HSPCs survival, such as Erg, Mecom, and Mpl. These data reveal that Nfix is a novel regulator of HSPCs survival posttransplantation and establish a role for Nfi genes in the regulation of this cellular compartment. |
