Transcription factor Hoxb5 reprograms B cells into functional T lymphocytes [RNA-Seq]. Mus musculus

Natural hematopoietic stem cells are currently the only cell resource to generate entire T lymphopoiesis in vivo. Altenatively, functional and non-tumorigenic T lymphocytes converted from the other cell types remain unsuccessful. Evidence is still lacking about the concept that 'lineage-switching factors' (LSFs) exist in HSC, whose re-activation in progeny cells can accomplish lineage conversions. Here we show that upon ectopic expression of Hoxb5(a HSC-specific transcription factor), the Pro-/Pre-B cells were induced into functional early T cell progenitors(iETPs) in vivo. The reprogramming process initiated in the bone marrow and accomplished in the thymus at ETP stage. Strikingly, the T lymphocytes derived from iETPs resemble their natural counterparts in transcriptome pattern, hierarchical differentiation, tissue distribution and immune functions. Our observations pave the way for achieving lineage regeneration by direct reprogramming autologous somatic cells in vivo. Further, our success in haematopoietic system may build a paradigm for LSF-mediated regeneration of other tissues. Overall design: Mus musculus mRNA profiles of 24 cell types, including HSC, MPP, Mature lineage cells (T cells_B cells_Myeloid cells), Pro-_Pre-_B cells, BM-ETPs, BM-iETPs, Thy-ETPs, Thy-iETPs, DN1, DN2, DN3, DN4, DP, CD4-SP,CD8-SP, iDN1, iDN2, iDN3, iDN4, iDP, iCD4-SP and iCD8-SP. 1000 of each cell type was sorted for RANseq analysis refered to published protocol (PMID:20203668).