Splicing in Hematopoietic Stem Cells

Hematopoietic Stem Cells (HSCs) are the source for all blood and immune cells. They also let life-saving bone-marrow transplantation. Understanding how HSCs keep multipotency and self-renew for life is of high interest, especially as perturbations of this regulation might cause malignancy. Expression profiles of all genes within HSCs had progressed our understanding in recent years. However, mammalian genes are mostly complexed, usually having more than one transcript per gene. Splicing into mRNA was not well analyzed in HSCs. We had mapped the whole transcriptome splicing in mouse HSCs, providing an essential resource. Our analysis also identified novel splicing events not previously described and demonstrated a possible functional difference between splice-variants of the same gene. Further data of splicing at the single-cell level is suggesting a novel discovery of HSC's heterogeneity. Importantly, splicing aberration had been associated with pre-leukemic state in human, thus we are collecting data from pre-malignant patients in order to improve diagnosis and possibly suggest novel treatments. The improved resolution of transcriptome splicing data is bringing a new dimension to understand HSCs, single-cell data further reveal the heterogeneity within normal or pre-malignant adult stem-cells.