Thy-1 Expression in Human Fibroblast Subsets Defines Myofibroblastic or Lipofibroblastic Phenotypes

• Published in: The American journal of pathology Vol. 163; no. 4; pp. 1291 - 1300
• Main Authors: Koumas, Laura, Smith, Terry J., Feldon, Steven, Blumberg, Neil, Phipps, Richard P.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.10.2003; ASIP; American Society for Investigative Pathology
• Subjects: Actins - metabolism; Biological and medical sciences; Blood Platelets - metabolism; Cell Differentiation - drug effects; Cell receptors; Cell structures and functions; Cells, Cultured; Female; Fibroblasts - classification; Fibroblasts - metabolism; Fibroblasts - physiology; Fundamental and applied biological sciences. Psychology; Humans; Interferon-gamma - pharmacology; Miscellaneous; Molecular and cellular biology; Muscle, Smooth - metabolism; Muscle, Smooth - pathology; Myometrium - cytology; Myometrium - metabolism; Orbit - cytology; Orbit - metabolism; Phenotype; Regular; Thy-1 Antigens - metabolism; Transforming Growth Factor beta - pharmacology; Up-Regulation - drug effects; Human; Immunohistochemistry; Cell culture; Myofibroblast; Fat storing cell; Cell differentiation; In vitro; Heterogeneity; Anatomic pathology; Molecular biology; Fibroblast; Subtype; Biological receptor
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)63488-8

Fibroblasts represent a dynamic population of cells, exhibiting functional heterogeneity within and among tissues. Fibroblast heterogeneity also results from phenotypic differences and may arise from activation or differentiation processes taking place in the cells. We previously reported that human fibroblasts were heterogeneous with respect to surface Thy-1 expression and that separation into Thy-1 + and Thy-1 − subsets resulted in functionally distinct subpopulations, leading to the concept of fibroblast subset specialization. In this report we investigated whether Thy-1 + and/or Thy-1 − fibroblasts were capable of differentiating into myofibroblasts or lipofibroblasts. Fibroblast subsets were used from human myometrium and orbit to test this hypothesis. Only Thy-1 + human myometrial and orbital fibroblasts were capable of myofibroblast differentiation after treatment with TGFβ or platelet concentrate supernatant, assessed by α smooth muscle actin expression. Interestingly, only Thy-1 −, but not Thy-1 + subsets differentiated to lipofibroblasts, as determined by the accumulation of cytoplasmic lipid droplets after treatment with 15-deoxy-Δ 12, 14-PGJ 2 or ciglitazone. We propose that fibroblast Thy-1 display pre-determines lineage to a contractile or lipid-like phenotype in the human myometrium and orbit. This additional distinction between Thy-1 + and Thy-1 − human fibroblast subtypes has important consequences in normal tissue homeostasis and in pathogenesis of orbital and myometrial diseases characterized by persistent myofibroblasts or fat accumulation, such as occurs in Graves' ophthalmopathy, tissue fibrosis, abnormal wound healing, and scarring.