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TIAM1 acts as an actin organization regulator to control adipose tissue–derived pericyte cell fate
Ginny Ching-Yun Hsu, … , Carol Morris, Aaron W. James
Ginny Ching-Yun Hsu, … , Carol Morris, Aaron W. James
Published May 23, 2023
Citation Information: JCI Insight. 2023;8(13):e159141. https://doi.org/10.1172/jci.insight.159141.
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Research Article Bone biology Cell biology

TIAM1 acts as an actin organization regulator to control adipose tissue–derived pericyte cell fate

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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.

Authors

Ginny Ching-Yun Hsu, Yiyun Wang, Amy Z. Lu, Mario A. Gomez-Salazar, Jiajia Xu, Dongqing Li, Carolyn Meyers, Stefano Negri, Sintawat Wangsiricharoen, Kristen Broderick, Bruno Peault, Carol Morris, Aaron W. James

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Figure 6

TIAM1 misexpression alters bone and adipose tissue generation after human pericyte xenotransplantation.

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TIAM1 misexpression alters bone and adipose tissue generation after hum...
TIAM1-KD or -OE pericytes or indicated control were implanted subcutaneously in the dorsum of adult athymic nude male mice (Charles River Laboratories strain code: 490) using a demineralized bone matrix carrier (3 million cells/50 mg DBX). Assessments were performed after 8 weeks. (A–K) TIAM1-KD pericyte implants in relation to scramble siRNA pericytes. (A) Representative 2-dimensional μCT images, (B) 3-dimensional μCT reconstructions, and quantification of (C) bone volume (BV) and (D) fractional bone volume (BV/TV). Histology by (E) H&E staining. (F) Osteocalcin (OCN) immunohistochemistry in red and human nuclei (HuNu) in green, with (G) OCN quantification. (H) Perilipin 1 (Plin1) immunohistochemistry in red and HuNu in green (yellow arrow points out cell coexpression of both OCN and HuNu) and (I) Plin1 quantification. (J–R) TIAM1 OE pericyte implants in relation to pCMV vector control pericytes. (J) Representative 2-dimensional μCT images, (K) 3-dimensional μCT reconstructions, and quantification of (L) BV and (M) BV/TV. Histology by (N) H&E staining. (O) OCN immunohistochemistry in red and HuNu in green, with (P) OCN quantification. (Q) Plin1 immunohistochemistry in red and HuNu in green, and (R) Plin1 quantification. Dotted white lines demarcate edges of the DBX area (“D”). Scale bar (all image panels): 20 μm. All quantitative data normalized to acellular control (DBX control). Each dot in the scatterplots represents an individual implantation site. N = 4 implants per group. *P < 0.05; **P < 0.01. Statistical analysis was performed using 2-sample Student’s t test.

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