Conversion of human fibroblasts into monocyte-like progenitor cells

authors

• Pulecio Julian
• Nivet Emmanuel
• Sancho-Martinez Ignacio
• Vitaloni Marianna
• Guenechea Guillermo
• Xia Yun
• Kurian Leo
• Dubova Ilir
• Bueren Juan
• Laricchia-Robbio Leopoldo
• Belmonte Juan Carlos Izpisua

keywords

• Animals
• Humans
• Mice
• Stem Cells
• Cell Differentiation
• Cell Lineage
• Antigens
• CD34
• Blood
• Cells
• Cultured
• Fibroblasts
• Leukocyte Common Antigens
• Macrophages
• MiRNAs
• Monocytes
• Reprogramming
• Transdifferentiation

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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