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Stem Cells. 2014 Nov;32(11):2923-2938. doi: 10.1002/stem.1800.

Conversion of human fibroblasts into monocyte-like progenitor cells.

Author information

1
Center of Regenerative Medicine in Barcelona, Dr. Aiguader, 88, 08003 Barcelona.
2
Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037 USA.
3
Hematopoiesis and Gene Therapy Division. Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT)/Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER). Madrid, Spain.
#
Contributed equally

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.

KEYWORDS:

Blood; Macrophages; Monocytes; Reprogramming; Transdifferentiation; miRNAs

PMID:
25175072
PMCID:
PMC4198469
DOI:
10.1002/stem.1800
[Indexed for MEDLINE]
Free PMC Article

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