| First Author | Laurenti E | Year | 2008 |
| Journal | Cell Stem Cell | Volume | 3 |
| Issue | 6 | Pages | 611-24 |
| PubMed ID | 19041778 | Mgi Jnum | J:149864 |
| Mgi Id | MGI:3849258 | Doi | 10.1016/j.stem.2008.09.005 |
| Citation | Laurenti E, et al. (2008) Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity. Cell Stem Cell 3(6):611-24 |
| abstractText | Myc activity is emerging as a key element in acquisition and maintenance of stem cell properties. We have previously shown that c-Myc deficiency results in accumulation of defective hematopoietic stem cells (HSCs) due to niche-dependent differentiation defects. Here we report that immature HSCs coexpress c-myc and N-myc mRNA at similar levels. Although conditional deletion of N-myc in the bone marrow does not affect hematopoiesis, combined deficiency of c-Myc and N-Myc (dKO) results in pancytopenia and rapid lethality. Interestingly, proliferation of HSCs depends on both myc genes during homeostasis, but is c-Myc/N-Myc independent during bone marrow repair after injury. Strikingly, while most dKO hematopoietic cells undergo apoptosis, only self-renewing HSCs accumulate the cytotoxic molecule Granzyme B, normally employed by the innate immune system, thereby revealing an unexpected mechanism of stem cell apoptosis. Collectively, Myc activity (c-Myc and N-Myc) controls crucial aspects of HSC function including proliferation, differentiation, and survival. |
