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SUMMARY:Mechanical signalling in stem cells and development - Dr Kevin Cha
 lut\, WT-MRC Cambridge Stem Cell Institute
DTSTART:20170118T160000Z
DTEND:20170118T170000Z
UID:TALK69177@talks.cam.ac.uk
CONTACT:Fiona Roby
DESCRIPTION:Stem cell culture has been characterised using soluble signals
  on tissue culture plastic\, providing a biochemical foundation for self-r
 enewal and differentiation. Nonetheless\, most previous stem cell research
  has overlooked the role of the extracellular matrix (ECM) and mechanical 
 signalling\, despite increasing evidence that they both mediate self-renew
 al and differentiation. To investigate the role of ECM and mechanical sign
 alling\, we have developed a novel hydrogel protocol that can be mechanica
 lly tuned\, ranging from embryo stiffness to skeletal stiffness\, while ma
 intaining control of ECM density. We can now present any combination of EC
 M molecules to cells with independent control over matrix density and stif
 fness. With our hydrogels\, we have explored mechanical and ECM signaling 
 in pluripotent stem cells and oligodendrocyte progenitor cells (OPCs). We 
 have shown\, in both mouse and human\, that we can maintain optimal naïve
  pluripotency using soft substrates with high ECM density\, while stiff su
 bstrates with identical ECM density drives differences in the actuation of
  growth factor signaling pathways that drive heterogeneity and differentia
 tion. We have also shown that we can reverse the loss of function associat
 ed with ageing and neurodegeneration in OPCs using soft substrates with hi
 gh ECM density. We will present a number of functional studies and a quant
 itative analysis of RNA sequencing datasets to support the conclusion that
  mechanics is an essential regulator of stem cell identity. Ultimately\, I
  will advance the hypothesis that mechanical sensing acts as a switch to m
 odulate growth factor signaling to support either self-renewal or differen
 tiation in stem cells. 
LOCATION:Lecture Theatre 2\, Department of Veterinary Medicine
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