Hematopoietic origins of fibroblasts: II. In vitro studies of fibroblasts, CFU-F, and fibrocytes.

Abstract:

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.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

Ebihara Y,Masuya M,Larue AC,Fleming PA,Visconti RP,Minamiguchi H,Drake CJ,Ogawa M

doi

10.1016/j.exphem.2005.10.008

keywords:

subject

Has Abstract

pub_date

2006-02-01 00:00:00

pages

219-29

issue

2

eissn

0301-472X

issn

1873-2399

pii

S0301-472X(05)00502-3

journal_volume

34

pub_type

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