title: Conversion of human fibroblasts into monocyte-like progenitor cells.
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.
authors.affiliation: Center of Regenerative Medicine in Barcelona, Dr. Aiguader, 88, 08003 Barcelona.
authors.forename: Julian
authors.initials: J
authors.lastname: Pulecio
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037 USA.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Nivet
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037 USA.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Sancho-Martinez
authors.affiliation: Center of Regenerative Medicine in Barcelona, Dr. Aiguader, 88, 08003 Barcelona.
authors.forename: Marianna
authors.initials: M
authors.lastname: Vitaloni
authors.affiliation: 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.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Guenechea
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037 USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037 USA.
authors.forename: Leo
authors.initials: L
authors.lastname: Kurian
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037 USA.
authors.forename: Ilir
authors.initials: I
authors.lastname: Dubova
authors.affiliation: 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.
authors.forename: Juan
authors.initials: J
authors.lastname: Bueren
authors.affiliation: Center of Regenerative Medicine in Barcelona, Dr. Aiguader, 88, 08003 Barcelona.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Laricchia-Robbio
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037 USA.
authors.forename: Juan Carlos Izpisua
authors.initials: JCI
authors.lastname: Belmonte
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*
chemical_list: D018952:Antigens, CD34; D017493:Leukocyte Common Antigens
keywords: Blood; Macrophages; Monocytes; Reprogramming; Transdifferentiation; miRNAs