Conversion of human fibroblasts into monocyte-like progenitor cells


  • 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


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


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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