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Postnatal origins of cardiac interstitial and valvular fibroblasts
Author(s) -
Visconti Richard P,
Ebihara Yasuhiro,
LaRue Amanda C,
Fleming Paul A,
Masuya Masahiro,
Minamiguchi Hitoshi,
Markwald Roger R,
Ogawa Makio,
Drake Chris J
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a846-c
Subject(s) - biology , haematopoiesis , bone marrow , population , stem cell , embryonic stem cell , microbiology and biotechnology , cd34 , pathology , immunology , medicine , genetics , environmental health , gene
Cardiac fibroblasts are believed to originate from the pro‐epicardial organ and endocardial cells that undergo an EMT during embryonic valve formation. To investigate contribution of circulating bone marrow hematopoietic stem cells (HSC) to the adult cardiac fibroblast population, we combined limited clonal expansion of single EGFP+, Lin‐, c‐kit+, Sca‐1+, CD34‐ bone marrow cells with transplantation of clonal populations into lethally irradiated congenic non‐EGFP mice. This strategy permits the potential of a single HSC to be evaluated in vivo. Analyses of cardiac tissues from mice with high levels of multilineage hematopoietic reconstitution revealed numerous EGFP+ cells within the cardiac ECM. Further, in response to myocardial infarction, HSC‐derived cells populated the infarct zone at high density compared to the viable myocardium. Based on our previous works demonstrating HSC contribution to other cell populations with fibroblastic/myofibroblastic properties (kidney mesangial and brain microglial cells), we evaluated fibroblastic phenotype in EGFP+ cells that had engrafted into the cardiac tissue. Our finding that a subpopulation of the EGFP+ cells expressed mRNA for procollagen 1α1 suggests that engrafted EGFP+ cells exhibit a differentiated phenotype not traditionally associated with the hematopoietic lineage. Y‐chromosome FISH analysis using female‐to‐male transplanted mice excluded fusion as a mechanism for HSC contribution to the cardiac fibroblast lineage. Collectively, these findings suggest that HSCs contribute to the cardiac fibroblast population during adult homeostasis and post‐infarction tissue remodeling. Supported by HL69123, HL52813, NCRR16434