TY - JOUR AU - Lis, Raphael AU - Karrasch, Charles C. AU - Poulos, Michael G. AU - Kunar, Balvir AU - Redmond, David AU - Duran, Jose G. Barcia AU - Badwe, Chaitanya R. AU - Schachterle, William AU - Ginsberg, Michael AU - Xiang, Jenny AU - Tabrizi, Arash Rafii AU - Shido, Koji AU - Rosenwaks, Zev AU - Elemento, Olivier AU - Speck, Nancy A. AU - Butler, Jason M. AU - Scandura, Joseph M. AU - Rafii, Shahin TI - Conversion of adult endothelium to immunocompetent haematopoietic stem cells JA - Nature PY - 2017/05/25/print VL - 545 IS - 7655 SP - 439 EP - 445 PB - Macmillan Publishers Limited, part of Springer Nature. All rights reserved. SN - 0028-0836 UR - http://dx.doi.org/10.1038/nature22326 L3 - 10.1038/nature22326 M3 - Article L3 - http://www.nature.com/nature/journal/v545/n7655/abs/nature22326.html#supplementary-information AB - Developmental pathways that orchestrate the fleeting transition of endothelial cells into haematopoietic stem cells remain undefined. Here we demonstrate a tractable approach for fully reprogramming adult mouse endothelial cells to haematopoietic stem cells (rEC-HSCs) through transient expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1 (collectively denoted hereafter as FGRS) and vascular-niche-derived angiocrine factors. The induction phase (days 0–8) of conversion is initiated by expression of FGRS in mature endothelial cells, which results in endogenous Runx1 expression. During the specification phase (days 8–20), RUNX1+ FGRS-transduced endothelial cells commit to a haematopoietic fate, yielding rEC-HSCs that no longer require FGRS expression. The vascular niche drives a robust self-renewal and expansion phase of rEC-HSCs (days 20–28). rEC-HSCs have a transcriptome and long-term self-renewal capacity similar to those of adult haematopoietic stem cells, and can be used for clonal engraftment and serial primary and secondary multi-lineage reconstitution, including antigen-dependent adaptive immune function. Inhibition of TGFβ and CXCR7 or activation of BMP and CXCR4 signalling enhanced generation of rEC-HSCs. Pluripotency-independent conversion of endothelial cells into autologous authentic engraftable haematopoietic stem cells could aid treatment of haematological disorders. ER -