Musashi-2 controls cell fate, lineage bias, and TGF-beta signaling in HSCs

作者：Park Sun Mi; Deering Raquel P; Lu Yuheng; Tivnan Patrick; Lianoglou Steve; Al Shahrour Fatima; Ebert Benjamin L; Hacohen Nir; Leslie Christina; Daley George Q; Lengner Christopher J; Kharas Michael G^*

来源：Journal of Experimental Medicine, 2014, 211(1): 71-87.

DOI：10.1084/jem.20130736

Hematopoietic stem cells (HSCs) are maintained through the regulation of symmetric and asymmetric cell division. We report that conditional ablation of the RNA-binding protein Msi2 results in a failure of HSC maintenance and engraftment caused by a loss of quiescence and increased commitment divisions. Contrary to previous studies, we found that these phenotypes were independent of Numb. Global transcriptome profiling and RNA target analysis uncovered Msi2 interactions at multiple nodes within pathways that govern RNA translation, stem cell function, and TGF-beta signaling. Msi2-null HSCs are insensitive to TGF-beta-mediated expansion and have decreased signaling output, resulting in a loss of myeloid-restricted HSCs and myeloid reconstitution. Thus, Msi2 is an important regulator of the HSC translatome and balances HSC homeostasis and lineage bias.

• 出版日期2014-1-13