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.
Original language | English (US) |
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Pages (from-to) | 2923-2938 |
Number of pages | 16 |
Journal | STEM CELLS |
Volume | 32 |
Issue number | 11 |
DOIs | |
State | Published - Nov 1 2014 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2014 AlphaMed Press.
Keywords
- Blood
- Macrophages
- Monocytes
- Reprogramming
- Transdifferentiation
- miRNAs
ASJC Scopus subject areas
- General Medicine