OBJECTIVE: Using transplantation of a clonal population of cells derived from a single hematopoietic stem cell (HSC) of transgenic enhanced green fluorescent protein (EGFP) mice, we have documented the hematopoietic origin of myofibroblasts, such as kidney mesangial cells and brain microglial cells. Because myofibroblasts are thought to be an activated form of fibroblasts, we tested the hypothesis that fibroblasts are derived from HSCs. MATERIALS AND METHODS: Clones of cells derived from single cells of EGFP Ly-5.2 C57Bl/6 mice were transplanted into lethally irradiated Ly-5.1 mice. Using bone marrow and peripheral blood cells from mice showing high-level multilineage hematopoietic reconstitution, we induced growth of fibroblasts in vitro. RESULTS: Culture of EGFP(+) bone marrow cells from clonally engrafted mice revealed adherent cells with morphology typical of fibroblasts. Flow cytometric analysis revealed that the majority of these cells are CD45(-) and express collagen-I and the collagen receptor, discoidin domain receptor 2 (DDR2). Reverse transcriptase polymerase chain reaction analysis of cultured cells demonstrated expression of procollagen 1-alpha1, DDR2, fibronectin, and vimentin mRNA. Fibroblast colonies consisting of EGFP(+) cells were observed in cultures of bone marrow cells from clonally engrafted mice, indicating an HSC origin of fibroblast colony-forming units. Culture of peripheral blood nucleated cells from clonally engrafted mice revealed EGFP(+) cells expressing collagen-I and DDR2, indicating that fibrocytes are also derived from HSCs. CONCLUSION: We conclude that a population of fibroblasts and their precursors are derived from HSCs.
OBJECTIVE: Using transplantation of a clonal population of cells derived from a single hematopoietic stem cell (HSC) of transgenic enhanced green fluorescent protein (EGFP) mice, we have documented the hematopoietic origin of myofibroblasts, such as kidney mesangial cells and brain microglial cells. Because myofibroblasts are thought to be an activated form of fibroblasts, we tested the hypothesis that fibroblasts are derived from HSCs. MATERIALS AND METHODS: Clones of cells derived from single cells of EGFP Ly-5.2 C57Bl/6 mice were transplanted into lethally irradiated Ly-5.1 mice. Using bone marrow and peripheral blood cells from mice showing high-level multilineage hematopoietic reconstitution, we induced growth of fibroblasts in vitro. RESULTS: Culture of EGFP(+) bone marrow cells from clonally engrafted mice revealed adherent cells with morphology typical of fibroblasts. Flow cytometric analysis revealed that the majority of these cells are CD45(-) and express collagen-I and the collagen receptor, discoidin domain receptor 2 (DDR2). Reverse transcriptase polymerase chain reaction analysis of cultured cells demonstrated expression of procollagen 1-alpha1, DDR2, fibronectin, and vimentin mRNA. Fibroblast colonies consisting of EGFP(+) cells were observed in cultures of bone marrow cells from clonally engrafted mice, indicating an HSC origin of fibroblast colony-forming units. Culture of peripheral blood nucleated cells from clonally engrafted mice revealed EGFP(+) cells expressing collagen-I and DDR2, indicating that fibrocytes are also derived from HSCs. CONCLUSION: We conclude that a population of fibroblasts and their precursors are derived from HSCs.
Authors: James J H Chong; Vashe Chandrakanthan; Munira Xaymardan; Naisana S Asli; Joan Li; Ishtiaq Ahmed; Corey Heffernan; Mary K Menon; Christopher J Scarlett; Amirsalar Rashidianfar; Christine Biben; Hans Zoellner; Emily K Colvin; John E Pimanda; Andrew V Biankin; Bin Zhou; William T Pu; Owen W J Prall; Richard P Harvey Journal: Cell Stem Cell Date: 2011-12-02 Impact factor: 24.633
Authors: Daniel L Worthley; Yiling Si; Michael Quante; Michael Churchill; Siddhartha Mukherjee; Timothy C Wang Journal: Exp Cell Res Date: 2013-03-13 Impact factor: 3.905
Authors: Keisuke Shirai; Yasuhiko Sera; William Bulkeley; Meenal Mehrotra; Omar Moussa; Amanda C LaRue; Dennis K Watson; Robert K Stuart; John Lazarchick; Makio Ogawa Journal: Exp Hematol Date: 2009-09-26 Impact factor: 3.084