TY - JOUR
T1 - TIAM1 acts as an actin organization regulator to control adipose tissue-derived pericyte cell fate
AU - Hsu, Ginny Ching Yun
AU - Wang, Yiyun
AU - Lu, Amy Z.
AU - Gomez-Salazar, Mario A.
AU - Xu, Jiajia
AU - Li, Dongqing
AU - Meyers, Carolyn
AU - Negri, Stefano
AU - Wangsiricharoen, Sintawat
AU - Broderick, Kristen
AU - Peault, Bruno
AU - Morris, Carol
AU - James, Aaron W.
N1 - Publisher Copyright:
Copyright: © 2023, Hsu et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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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U2 - 10.1172/jci.insight.159141
DO - 10.1172/jci.insight.159141
M3 - Article
C2 - 37219951
AN - SCOPUS:85164272244
SN - 2379-3708
VL - 8
JO - JCI Insight
JF - JCI Insight
IS - 13
M1 - e159141
ER -