TY - JOUR
T1 - Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment
AU - McBeath, Rowena
AU - Pirone, Dana M.
AU - Nelson, Celeste M.
AU - Bhadriraju, Kiran
AU - Chen, Christopher S.
N1 - Funding Information:
This work was supported in part by NIGMS (GM 60692) and NIBIB (EB 00262). R.M. acknowledges support from the NIH Medical Scientist Training Program. D.M.P. was supported in part by the Ruth L. Kirschstein National Research Service Award HL 076060-01. C.M.N. acknowledges support from the Whitaker Foundation. We thank M. Philips and P. Burbelo for the RhoA and GFP constructs, and are grateful to S. Sharkis, A. Saiardi, J. Tan, and D. Gray for helpful discussions.
PY - 2004/4
Y1 - 2004/4
N2 - 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.
AB - 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.
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U2 - 10.1016/S1534-5807(04)00075-9
DO - 10.1016/S1534-5807(04)00075-9
M3 - Article
C2 - 15068789
AN - SCOPUS:1842426730
SN - 1534-5807
VL - 6
SP - 483
EP - 495
JO - Developmental cell
JF - Developmental cell
IS - 4
ER -