28 March 2019

Specifying the Pancreatic Islet through Biomechanical Forces

commentary in New England Journal of Medicine

Clinical Implications of Basic Research, based on Mamidi et al. Mechanosignalling via integrins directs fate decisions of pancreatic progenitors published November 28, 2018, in Nature 

Based on Ondine Cleaver commentary. 

In this commentary on a recent paper published in the journal Nature by the Semb group*, Ondine Cleaver describes how living cells respond to physical forces, including those relayed from the complex cellular and extracellular microenvironment within a tissue addressed in this study.

Briefly, from the Semb group at DanStem, Mamidi et al. in their recent study examined developing pancreatic cells and found that changes in the extracellular milieu trigger intracellular cytoskeletal dynamics and transcriptional changes that profoundly affect the “decision” by cells to differentiate into islet endocrine cells. By manipulating the culture conditions of human embryonic stem cells, as well as by using gain and loss-of-function approaches both in vivo and in vitro, the authors showed that biomechanical signaling pathways drive cell-fate decisions in pancreatic cell types.

The commentary emphases** that as researchers continue to refine their understanding of how functional beta cells differentiate in vivo, they are at the same time creating a road map that could be used to eventually recapitulate, either in vitro or in vivo, the molecular events that direct progenitors to differentiate into islet endocrine cells.

*Mamidi, A., Prawiro, C., Seymour, P.A., de Lichtenberg, K.H., Jackson, A., Serup, P., and Semb, H. (2018). Mechanosignalling via integrins directs fate decisions of pancreatic progenitorsNature, doi: 10.1038/s41586-018-0762-2

**Ondine Cleaver the Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas.DOI: 10.1056/NEJMcibr1900052 Copyright © 2019 Massachusetts Medical Society.

The New England Journal of Medicine is a weekly medical journal published by the Massachusetts Medical Society. It is among the most prestigious peer-reviewed medical journals as well as the oldest continuously published one.

Link to the commentary