Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment

被引：3301

作者：

McBeath, R

Pirone, DM

Nelson, CM

Bhadriraju, K

Chen, CS ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Cellular & Mol Med Program, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA

来源：

DEVELOPMENTAL CELL | 2004年 / 6卷 / 04期

关键词：

D O I：

10.1016/S1534-5807(04)00075-9

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Commitment of stem cells to different lineages is regulated by many cues in the local tissue microenvironment. Here we demonstrate that cell shape regulates commitment of human mesenchymal stem cells (hMSCs) to adipocyte or osteoblast fate. hMSCs allowed to adhere, flatten, and spread underwent osteogenesis, while unspread, round cells became adipocytes. Cell shape regulated the switch in lineage commitment by modulating endogenous RhoA activity. Expressing dominant-negative RhoA committed hMSCs to become adipocytes, while constitutively active RhoA caused osteogenesis. However, the RhoA-mediated adipogenesis or osteogenesis was conditional on a round or spread shape, respectively, while constitutive activation of the RhoA effector, ROCK, induced osteogenesis independent of cell shape. This RhoA-ROCK commitment signal required actin-myosin-generated tension. These studies demonstrate that mechanical cues experienced in developmental and adult contexts, embodied by cell shape, cytoskeletal tension, and RhoA signaling, are integral to the commitment of stem cell fate.

引用

页码：483 / 495

页数：13

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