RT Journal Article
SR Electronic
T1 Transgene-free hematopoietic stem and progenitor cells from human induced pluripotent stem cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 177691
DO 10.1101/177691
A1 Laurence Guyonneau-Harmand
A1 Bruno L’Homme
A1 Brigitte Birebent
A1 Christophe Desterke
A1 Nathalie Chevallier
A1 Loïc Garçon
A1 Hélène Lapillonne
A1 Marc Benderitter
A1 François Delhommeau
A1 Thierry Jaffredo
A1 Alain Chapel
A1 Luc Douay
YR 2017
UL http://biorxiv.org/content/early/2017/08/21/177691.abstract
AB The successful production of Hematopoietic Stem and Progenitor Cells (HSPCs) from human pluripotent sources is conditioned by transgene delivery1-5. We describe here a dedicated and tractable one step, GMP-grade, transgene-free and stroma-free protocol to produce HSPCs from human induced pluripotent stem cells (hiPSCs). This procedure, applied to several sources of hiPSCs with equal efficiency, is based on a directed differentiation with morphogens and cytokines to generate a cell population close to nascent HSPCs or their immediate forerunners i.e., hemogenic endothelial cells6-9. Following engraftment into immunocompromised recipients, this cell population was proved capable of a robust myeloid, lymphoid and definitive red blood cell production in sequential recipients for at least 40 weeks. Further identification of the repopulating cells show that they express the G protein–coupled receptor APELIN (APLNR) and the homing receptor CXCR4. This demonstrates that the generation of bona fide HSPCs from hiPSCs without transgenes is possible and passes through an early endo-hematopoietic intermediate. This work opens the way to the generation of clinical grade HSPCs for the treatment of hematological diseases and holds promise for the analysis of HSPC development in the human species.