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TIAM1 acts as an actin organization regulator to control adipose tissue-derived pericyte cell fate.
Hsu, Ginny Ching-Yun; Wang, Yiyun; Lu, Amy Z; Gomez-Salazar, Mario A; Xu, Jiajia; Li, Dongqing; Meyers, Carolyn; Negri, Stefano; Wangsiricharoen, Sintawat; Broderick, Kristen; Peault, Bruno; Morris, Carol; James, Aaron W.
Afiliación
  • Hsu GC; Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
  • Wang Y; Department of Orthodontics, Oregon Health & Science University, Portland, Oregon, USA.
  • Lu AZ; Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
  • Gomez-Salazar MA; Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
  • Xu J; Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
  • Li D; Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
  • Meyers C; Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
  • Negri S; Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
  • Wangsiricharoen S; Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
  • Broderick K; Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
  • Peault B; Department of Plastic Surgery, Johns Hopkins University, Baltimore, Maryland, USA.
  • Morris C; UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and Orthopaedic Hospital Research Center, Los Angeles, California, USA.
  • James AW; Center for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom.
JCI Insight ; 8(13)2023 07 10.
Article en En | MEDLINE | ID: mdl-37219951
ABSTRACT
Pericytes are multipotent mesenchymal precursor cells that demonstrate tissue-specific properties. In this study, by comparing human adipose tissue- and periosteum-derived pericyte microarrays, we identified T cell lymphoma invasion and metastasis 1 (TIAM1) as a key regulator of cell morphology and differentiation decisions. TIAM1 represented a tissue-specific determinant between predispositions for adipocytic versus osteoblastic differentiation in human adipose tissue-derived pericytes. TIAM1 overexpression promoted an adipogenic phenotype, whereas its downregulation amplified osteogenic differentiation. These results were replicated in vivo, in which TIAM1 misexpression altered bone or adipose tissue generation in an intramuscular xenograft animal model. Changes in pericyte differentiation potential induced by TIAM1 misexpression correlated with actin organization and altered cytoskeletal morphology. Small molecule inhibitors of either small GTPase Rac1 or RhoA/ROCK signaling reversed TIAM1-induced morphology and differentiation in pericytes. In summary, our results demonstrate that TIAM1 regulates the cellular morphology and differentiation potential of human pericytes, representing a molecular switch between osteogenic and adipogenic cell fates.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Actinas / Pericitos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: JCI Insight Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Actinas / Pericitos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: JCI Insight Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos