title: Identification of a Hematopoietic Cell Dedifferentiation-Inducing Factor.
abstract: It has long been realized that hematopoietic cells may have the capacity to trans-differentiate into non-lymphohematopoietic cells under specific conditions. However, the mechanisms and the factors for hematopoietic cell trans-differentiation remain unknown. In an in vitro culture system, we found that using a conditioned medium from proliferating fibroblasts can induce a subset of hematopoietic cells to become adherent fibroblast-like cells (FLCs). FLCs are not fibroblasts nor other mesenchymal stromal cells, based on their expression of type-1 collagen, and other stromal cell marker genes. To identify the active factors in the conditioned medium, we cultured fibroblasts in a serum-free medium and collected it for further purification. Using the fractions from filter devices of different molecular weight cut-offs, and ammonium sulfate precipitation collected from the medium, we found the active fraction is a protein. We then purified this fraction by using fast protein liquid chromatography (FPLC) and identified it by mass spectrometer as macrophage colony-stimulating factor (M-CSF). The mechanisms of M-CSF-inducing trans-differentiation of hematopoietic cells seem to involve a tyrosine kinase signalling pathway and its known receptor. The FLCs express a number of stem cell markers including SSEA-1 and -3, OCT3/4, NANOG, and SOX2. Spontaneous and induced differentiation experiments confirmed that FLCs can be further differentiated into cell types of three germ layers. These data indicate that hematopoietic cells can be induced by M-CSF to dedifferentiate to multipotent stem cells. This study also provides a simple method to generate multipotent stem cells for clinical applications.
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Yunyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Vancouver Prostate Centre, Vancouver, British Columbia, Canada.
authors.forename: Hans
authors.initials: H
authors.lastname: Adomat
authors.affiliation: Vancouver Prostate Centre, Vancouver, British Columbia, Canada.
authors.forename: Emma Tomlinson
authors.initials: ET
authors.lastname: Guns
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Payman
authors.initials: P
authors.lastname: Hojabrpour
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Duronio
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Terry-Ann
authors.initials: TA
authors.lastname: Curran
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Reza Baradar
authors.initials: RB
authors.lastname: Jalili
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.|Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: William
authors.initials: W
authors.lastname: Jia
authors.affiliation: Department of Experimental Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Zahid
authors.initials: Z
authors.lastname: Delwar
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Sanam Salimi
authors.initials: SS
authors.lastname: Elizei
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Aziz
authors.initials: A
authors.lastname: Ghahary
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D019070:Cell Lineage; D049109:Cell Proliferation; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism; D019899:Paracrine Communication; D010641:Phenotype; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D007328:Insulin; D049452:Green Fluorescent Proteins; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor