Conversion of human fibroblasts into monocyte-like progenitor cells

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

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 languageEnglish (US)
Pages (from-to)2923-2938
Number of pages16
JournalStem Cells
Volume32
Issue number11
DOIs
StatePublished - Nov 1 2014

Keywords

  • Blood
  • Macrophages
  • Monocytes
  • Reprogramming
  • Transdifferentiation
  • miRNAs

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Conversion of human fibroblasts into monocyte-like progenitor cells'. Together they form a unique fingerprint.

Cite this