Transgelin is a TGFβ-inducible gene that regulates osteoblastic and adipogenic differentiation of human skeletal stem cells through actin cytoskeleston organization.
Transgelin is a TGFβ-inducible gene that regulates osteoblastic and adipogenic differentiation of human skeletal stem cells through actin cytoskeleston organization.
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Transgelin是一种TGFβ诱导的基因，可通过肌动蛋白Cytoskeleston组织调节人骨骼干细胞的成骨细胞和成糖分化。
DOI：
10.1038/cddis.2016.196
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发表时间：
2016-08-04
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
再生医学是一种治疗需要增强骨再生的疾病的新方法。我们鉴定了transgelin（TAGLN），一种转化生长因子β（TGFβ）诱导基因，在人骨髓源性基质（骨骼）干细胞（hMSC）体外成骨细胞和脂肪细胞分化过程中作为上调基因。siRNA介导的TAGLN基因沉默损害了成骨细胞和脂肪细胞的谱系分化，但增强了细胞增殖。另外的功能研究表明，TAGLN缺陷损害hMSC细胞运动性和体外transwell细胞迁移。另一方面，TAGLN过表达降低了hMSC细胞增殖，但增强了细胞迁移、成骨细胞和脂肪细胞分化以及体内骨形成。此外，缺乏或过度表达的TAGLN在hMSC与细胞和核形态和细胞质细胞器组成的显着变化，高含量成像和透射电子显微镜显示，肌动蛋白丝的分布和细胞骨架组织的变化显着改变所证明的。TAGLN缺陷型hMSC的分子特征显示，与细胞分化相关的几个基因和遗传途径，包括肌动蛋白细胞骨架和粘着斑途径的调节，被下调。我们的数据表明，TAGLN具有通过调节细胞骨架组织从未分化的hMSC产生定向祖细胞的作用。靶向TAGLN是富集再生医学应用所需的定向hMSC细胞的合理方法。
Regenerative medicine is a novel approach for treating conditions in which enhanced bone regeneration is required. We identified transgelin (TAGLN), a transforming growth factor beta (TGFβ)-inducible gene, as an upregulated gene during in vitro osteoblastic and adipocytic differentiation of human bone marrow-derived stromal (skeletal) stem cells (hMSC). siRNA-mediated gene silencing of TAGLN impaired lineage differentiation into osteoblasts and adipocytes but enhanced cell proliferation. Additional functional studies revealed that TAGLN deficiency impaired hMSC cell motility and in vitro transwell cell migration. On the other hand, TAGLN overexpression reduced hMSC cell proliferation, but enhanced cell migration, osteoblastic and adipocytic differentiation, and in vivo bone formation. In addition, deficiency or overexpression of TAGLN in hMSC was associated with significant changes in cellular and nuclear morphology and cytoplasmic organelle composition as demonstrated by high content imaging and transmission electron microscopy that revealed pronounced alterations in the distribution of the actin filament and changes in cytoskeletal organization. Molecular signature of TAGLN-deficient hMSC showed that several genes and genetic pathways associated with cell differentiation, including regulation of actin cytoskeleton and focal adhesion pathways, were downregulated. Our data demonstrate that TAGLN has a role in generating committed progenitor cells from undifferentiated hMSC by regulating cytoskeleton organization. Targeting TAGLN is a plausible approach to enrich for committed hMSC cells needed for regenerative medicine application.
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DOI：
10.1016/j.bbrc.2004.11.059
发表时间：
2005-01-21
影响因子：
3.1
作者：
Abdallah, BM;Haack-Sorensen, M;Kassem, M
通讯作者：
Kassem, M
影响因子：
3.3
作者：
Erlebacher, A;Filvaroff, EH;Derynck, R
通讯作者：
Derynck, R
影响因子：
1.2
作者：
Chen, Li;Shi, Kaikai;Kassem, Moustapha
通讯作者：
Kassem, Moustapha
影响因子：
6.2
作者：
Harmey, D;Stenbeck, G;Grigoriadis, AE
通讯作者：
Grigoriadis, AE
影响因子：
14.9
作者：
Chen, SY;Kulik, M;Lechleider, RJ
通讯作者：
Lechleider, RJ