Editing Cellular differentiation (section)

=== Effect of matrix elasticity ===
In order to fulfill the purpose of regenerating a variety of tissues, adult stems are known to migrate from their niches, adhere to new extracellular matrices (ECM) and differentiate. The ductility of these microenvironments are unique to different tissue types. The ECM surrounding brain, muscle and bone tissues range from soft to stiff. The transduction of the stem cells into these cells types is not directed solely by chemokine cues and cell to cell signaling. The elasticity of the microenvironment can also affect the differentiation of mesenchymal stem cells (MSCs which originate in bone marrow.) When MSCs are placed on substrates of the same stiffness as brain, muscle and bone ECM, the MSCs take on properties of those respective cell types.<ref name=":0">{{cite journal | vauthors = Engler AJ, Sen S, Sweeney HL, Discher DE | title = Matrix elasticity directs stem cell lineage specification | journal = Cell | volume = 126 | issue = 4 | pages = 677–689 | date = August 2006 | pmid = 16923388 | doi = 10.1016/j.cell.2006.06.044 | s2cid = 16109483 | doi-access = free }}</ref>
Matrix sensing requires the cell to pull against the matrix at focal adhesions, which triggers a cellular mechano-transducer to generate a signal to be informed what force is needed to deform the matrix. To determine the key players in matrix-elasticity-driven lineage specification in MSCs, different matrix microenvironments were mimicked. From these experiments, it was concluded that focal adhesions of the MSCs were the cellular mechano-transducer sensing the differences of the matrix elasticity. The non-muscle myosin IIa-c isoforms generates the forces in the cell that lead to signaling of early commitment markers. Nonmuscle myosin IIa generates the least force increasing to non-muscle myosin IIc. There are also factors in the cell that inhibit non-muscle myosin II, such as [[blebbistatin]]. This makes the cell effectively blind to the surrounding matrix.<ref name=":0" /> Researchers have achieved some success in inducing stem cell-like properties in HEK 239 cells by providing a soft matrix without the use of diffusing factors.<ref>{{cite journal | vauthors = Guo J, Wang Y, Sachs F, Meng F | title = Actin stress in cell reprogramming | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 49 | pages = E5252–E5261 | date = December 2014 | pmid = 25422450 | pmc = 4267376 | doi = 10.1073/pnas.1411683111 | bibcode = 2014PNAS..111E5252G | doi-access = free | author-link3 = Frederick Sachs }}</ref> The stem-cell properties appear to be linked to tension in the cells' actin network. One identified mechanism for matrix-induced differentiation is tension-induced proteins, which remodel chromatin in response to mechanical stretch.<ref>{{cite journal | vauthors = Guilak F, Cohen DM, Estes BT, Gimble JM, Liedtke W, Chen CS | title = Control of stem cell fate by physical interactions with the extracellular matrix | journal = Cell Stem Cell | volume = 5 | issue = 1 | pages = 17–26 | date = July 2009 | pmid = 19570510 | pmc = 2768283 | doi = 10.1016/j.stem.2009.06.016 }}</ref> The RhoA pathway is also implicated in this process.<ref>{{cite journal | vauthors = Vining KH, Mooney DJ | title = Mechanical forces direct stem cell behaviour in development and regeneration | journal = Nature Reviews. Molecular Cell Biology | volume = 18 | issue = 12 | pages = 728–742 | date = December 2017 | pmid = 29115301 | pmc = 5803560 | doi = 10.1038/nrm.2017.108 }}</ref>