Force-Type Dependent Mechanotransduction in Mesenchymal Stromal Cells (Mscs) Mediated by Mechanosensitive Channel Transient Receptor Potential Melastatin 7 (Trpm7)

  • Liu, Yi-Shiuan (PI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

Mesenchymal stromal cells (MSCs) are adult stem cells of stromal origin which are capable of self-renewal and differentiation into diverse specialized cell types. MSC has great potential in cell therapy and regenerative medicine due to its multipotency and immunomodulatory property. Other than chemical induction, physical properties of the microenvironments as well as mechanical force can regulate stem cells' phenotypes. Transient receptor potential melastatin 7 (TRPM7) is a non-selective cation channel mechanosensitive to fluid shear stress and pressure loading. TRPM7 acts as a mediator of MSC osteogenic differentiation and is involved in many physiological processes, including arterial calcification, immune homeostasis, as well as cancer progression. However, the underlying molecular mechanisms of TRPM7 related to mechanotransduction in MSCs remain elusive. The aim of this proposed study is to decipher the mechanotransduction signaling pathways mediated by TRPM7. I will first identify several force-type specific mechanosensitive channels (MsChs) that are activated by shear stress, pressure loading or compression/stretch and then investigate the roles of these MsChs in MSC differentiation. Time series mechano-sensitive phosphoproteomic profiles from differentiating MSCs upon mechanical stimuli will be deconvoluted from mechano-insensitive ones from MsCh-knockdown MSCs to pinpoint signaling signatures of mechanotransduction. Focus of the current study will be primarily on TRPM7-related mechanotransduction. The binding partners of TRPM7 kinase domains will be identified as well. Finally, I will screen early mechano-responders which can modulate MsChs function for potential drug targets. Using MSC as a model system to understand the roles of TRPM7 in mechanotransduction will provide insight into developing therapeutic strategies regarding tissue engineering, regenerative medicine, and perhaps cancer treatment.

Project IDs

Project ID:PC10905-0021
External Project ID:MOST109-2314-B182-010
StatusFinished
Effective start/end date01/06/2031/05/21

Keywords

  • Transient receptor potential melastatin 7 (TRPM7)
  • Mesenchymal stromal cells (MSCs)
  • Mechanotransduction
  • Mechanosensitive channels (MsChs)
  • Osteogenic differentiation
  • Shear stress.

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