Article

Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity.

Ecole Polytechnique Fédérale de Lausanne (EPFL), ISREC, Swiss Institute for Experimental Cancer Research, School of Life Science, CH-1066 Epalinges, Switzerland.
Cell stem cell (Impact Factor: 23.56). 01/2009; 3(6):611-24. DOI: 10.1016/j.stem.2008.09.005
Source: PubMed

ABSTRACT 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.

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