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Identification of a Hematopoietic Cell Dedifferentiation‐Inducing Factor
Author(s) -
Li Yunyuan,
Adomat Hans,
Guns Emma Tomlinson,
Hojabrpour Payman,
Duronio Vincent,
Curran TerryAnn,
Jalili Reza Baradar,
Jia William,
Delwar Zahid,
Zhang Yun,
Elizei Sanam Salimi,
Ghahary Aziz
Publication year - 2016
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25239
Subject(s) - sox2 , stem cell , stromal cell , microbiology and biotechnology , homeobox protein nanog , haematopoiesis , biology , multipotent stem cell , cellular differentiation , stem cell factor , mesenchymal stem cell , chemistry , induced pluripotent stem cell , cancer research , progenitor cell , embryonic stem cell , biochemistry , gene
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. J. Cell. Physiol. 231: 1350–1363, 2016. © 2015 Wiley Periodicals, Inc.