Hematopoietic stem cells lacking Ott1 display aspects associated with aging and are unable to maintain quiescence during proliferative stress

The infant leukemia-associated gene, Ott1 (Rbm15), has broad regulatory effects on embryonic development and hematopoiesis. Embryonic deletion of Ott1 results in defects to the placenta, spleen and heart. Conditional deletion within the adult hematopoietic compartment demonstrates a requirement in pre-B development and inhibitory roles in myeloid progenitor and megakaryocyte populations. Ott1-deleted bone marrow has an expansion of the Lin- Sca-1+ c-Kit+ (LSK) population which includes the hematopoietic stem cell (HSC) population. Functional HSC testing through competitive repopulation of irradiated recipients demonstrated however, a severe defect in Ott1-deficient HSCs, despite adequate numbers of immunophenotypically identified long term HSCs. Although mice deleted in situ for Ott1 are able to maintain hematopoiesis in steady state over a normal lifetime, but when subjected to proliferative stress, the HSC population loses the self-renewing, G0 fraction and undergoes bone marrow failure.

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Xiao N, Jani K, Morgan K, Okabe R, Cullen DE, Jesneck JL, Raffel GD