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Conversion of human fibroblasts into monocyte-like progenitor cells

Abstract : Reprogramming technologies have emerged as a promising approach for future regenerative medicine. Here, we report on the establishment of a novel methodology allowing for the conversion of human fibroblasts into hematopoietic progenitor-like cells with macrophage differentiation potential. SOX2 overexpression in human fibroblasts, a gene found to be upregulated during hematopoietic reconstitution in mice, induced the rapid appearance of CD34+ cells with a concomitant upregulation of mesoderm-related markers. Profiling of cord blood hematopoietic progenitor cell populations identified miR-125b as a factor facilitating commitment of SOX2-generated CD34+ cells to immature hematopoietic-like progenitor cells with grafting potential. Further differentiation toward the monocytic lineage resulted in the appearance of CD14+ cells with functional phagocytic capacity. In vivo transplantation of SOX2/miR-125b-generated CD34+ cells facilitated the maturation of the engrafted cells toward CD45+ cells and ultimately the monocytic/macrophage lineage. Altogether, our results indicate that strategies combining lineage conversion and further lineage specification by in vivo or in vitro approaches could help to circumvent long-standing obstacles for the reprogramming of human cells into hematopoietic cells with clinical potential.
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https://hal.archives-ouvertes.fr/hal-01736193
Contributor : Denis Becquet <>
Submitted on : Friday, March 16, 2018 - 4:38:02 PM
Last modification on : Wednesday, September 16, 2020 - 4:33:56 PM

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Julian Pulecio, Emmanuel Nivet, Ignacio Sancho-Martinez, Marianna Vitaloni, Guillermo Guenechea, et al.. Conversion of human fibroblasts into monocyte-like progenitor cells. Stem cells (Dayton, Ohio), 2014, 32 (11), pp.2923--2938. ⟨10.1002/stem.1800⟩. ⟨hal-01736193⟩

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