RNA sequencing of WT and Srp72+/- LT-HSCs from aged mice

To investigat the role of Srp72 in hematopoiesis and the development of myelodysplasia and bone marrow aplasia, we generated a transgenic mouse strain with a Srp72 KO strand. Heterozygous loss of SRP72 in mice is not associated with major changes in steady-state hematopoiesis, although we did observe mild reductions in peripheral blood and BM cellularity. Moreover, we also detected minor changes within the stem/progenitor compartment as well as in their propensity to generate a balanced lineage output. We did not observe the development of any haematological disorder, thus the Srp72+/- mouse model only partially recapitulates the more severe aplasia and myelodysplasia observed in families with inherited SRP72 lesions. We thereafter extracted RNA from LT-HSCs of old mice to observe transcriptional changes in those mice. Interestingly, gene expression analysis demonstrated that genes encoding secreted factors, including cytokines and cell-surface receptors, were transcriptionally down-regulated in Srp72+/- animals. This can potentially provide mechanistic insights into why SRP72 lesions are associated with the development of severe aplasia and myelodysplasia in humans. Overall design: RNA sequencing of LT-HSCs from 4 WT and 3 Srp72+/- aged mice