SRP067667 PRJNA306698 GSE76243 IMP1 re-expression in adult hematopoietic stem cells RNA Sequencing The onco-fetal RNA-binding protein IMP1 is expressed in fetal liver HSCs, but down-regulated in adult BM HSCs. We here show that when IMP1 is re-expressed in adult HSCs it induces a significant part of the fetal HSC gene expression signature. In addition, IMP1 re-expression leads to the expansion of phenotypic long term (LT-)HSCs, and increased generation of fetal peritoneal B1a B-cells and thymic ?d-T-cells. Finally, IMP1 expressing adult LT-HSCs show dramatically improved self-renewal in serial transplantations compared to their normal counterparts. To assess the effect of IMP1 re-expression on the molecular properties of adult HSCs we performed RNA sequencing of total RNA isolated from Control and IMP1 HSCs sorted from primary recipient mice, transplanted with control or IMP1+ total bone marrow cells. Overall design: To achieve re-expression of IMP1 in adult mice we generated a conditional knock-in of IMP1 into the Rosa26 locus. In order to achieve selective IMP1 re-expression in hematopoietic cells, we transplanted whole bone marrow (CD45.2 allotype) from Rosa26II+;Mx1-Cretg/+ (IMP1 mice) and Rosa26+I+;Mx1-Cretg/+ (Control mice) into lethally irradiated CD45.1/2 mice. The expression of IMP1 was then induced by inducing the expression of the Mx1-Cre transgene by poly(I-C) injection. For RNA sequencing 200 CD45.2+ LT-HSCs, were sorted from primary recipients, 8 weeks after last PolyIC injection, directly into lysis buffer supplemented with RNase Inhibitor (Clontech). 3 biological replicates were generated from each genotype. Samples were prepared using the SMARTer™ Ultra Low RNA kit for Illumina Sequencing (Clontech) as previously described (Ramskold et al., 2012) GSE76243