Cell Shape, Cytoskeletal Tension, and RhoA Regulate Stem Cell Lineage Commitment
Cell Shape, Cytoskeletal Tension, and RhoA Regulate Stem Cell Lineage Commitment
Rowena McBeath, Dana M. Pirone, Celeste M. Nelson, Kiran Bhadriraju, and Christopher S. Chen.
Developmental Cell, Vol. 6, 483–495, April, 2004.
Summary:
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 integrato the commitment of stem cell fate.
I find this paper really interesting because it demonstrates how physical cues like island size affects cell shape, which in turn affects cell's ability to make decisions about its fate. The authors showed that cell shape acts as a mechanical cue in driving hMSC commitment to osteoblasts vs. adipocytes. I also liked how the authors were able to study the transduction of these physical signals into biochemical processes by doing constitutively active/inactive experiments. Additionally, the authors use techniques such as micro-island patterning, FACS, RT-PCR, recombinant adenovirus constructs etc. to study this bioengineering problem.
Here is the link for google scholar:
http://scholar.google.com/scholar?q=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1534580704000759&hl=en&lr=&btnG=Search
3 comments:
What are the physical cues associated with island size? If the cell has no built-in "ruler", what does the island size and shape change that the cell can detect?
What about cells that are flat but express active RhoA or cells constitutively expressing RhoA yet in an environment telling the cells to differentiate into adipocytes? Basically, when the cells meet two contradicting environmental or mechanical cues, which one will dominate?
It's always interesting to examine whether cell fate is predetermined or can be altered by environmental conditions.
However, what is be examined here is actually conditions of the cell itself: shape, cytoskeletal tension, and endogenous RhoA activity. Thus, could it be that the cell creates a particular shape, cytoskeletal tension, or codes fo a particular RhoA activity level to govern it's own cell lineage commitment?
Post a Comment