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TIAM1 作为一种肌动蛋白组织调节剂，控制脂肪组织衍生的周细胞命运。

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

机构信息

Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.

Department of Orthodontics, Oregon Health & Science University, Portland, Oregon, USA.

出版信息

JCI Insight. 2023 Jul 10;8(13):e159141. doi: 10.1172/jci.insight.159141.

DOI:10.1172/jci.insight.159141
PMID:37219951
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10371340/
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.

摘要

周细胞是多能间充质前体细胞，具有组织特异性。在这项研究中，通过比较人脂肪组织和骨膜来源的周细胞微阵列，我们发现 T 细胞淋巴瘤侵袭和转移 1（TIAM1）是细胞形态和分化决策的关键调节因子。TIAM1 代表了人脂肪组织来源的周细胞中脂肪细胞分化与成骨细胞分化之间的倾向性的组织特异性决定因素。TIAM1 的过表达促进了脂肪生成表型，而其下调则增强了成骨分化。这些结果在体内得到了复制，在肌内异种移植动物模型中，TIAM1 的异常表达改变了骨或脂肪组织的生成。TIAM1 异常表达诱导的周细胞分化潜能的变化与肌动蛋白组织和细胞骨架形态的改变相关。小 GTPase Rac1 或 RhoA/ROCK 信号的小分子抑制剂逆转了 TIAM1 诱导的周细胞形态和分化。总之，我们的结果表明，TIAM1 调节人周细胞的细胞形态和分化潜能，代表了成骨细胞和脂肪细胞命运之间的分子开关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468c/10371340/ba4ef0277ad0/jciinsight-8-159141-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468c/10371340/fd03b7685155/jciinsight-8-159141-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468c/10371340/f1eeb836a0fc/jciinsight-8-159141-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468c/10371340/b14e2cf85f88/jciinsight-8-159141-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468c/10371340/65bbee59851e/jciinsight-8-159141-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468c/10371340/184ecd3fd1ae/jciinsight-8-159141-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468c/10371340/ba4ef0277ad0/jciinsight-8-159141-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468c/10371340/fd03b7685155/jciinsight-8-159141-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468c/10371340/f1eeb836a0fc/jciinsight-8-159141-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468c/10371340/b14e2cf85f88/jciinsight-8-159141-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468c/10371340/65bbee59851e/jciinsight-8-159141-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468c/10371340/184ecd3fd1ae/jciinsight-8-159141-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/468c/10371340/ba4ef0277ad0/jciinsight-8-159141-g015.jpg

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