Asset Details
Do you wish to reserve the book?
Mechanosignalling via integrins directs fate decisions of pancreatic progenitors
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Mechanosignalling via integrins directs fate decisions of pancreatic progenitors
Do you wish to request the book?
Mechanosignalling via integrins directs fate decisions of pancreatic progenitors
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Mechanosignalling via integrins directs fate decisions of pancreatic progenitors
2018
Overview
The pancreas originates from two epithelial evaginations of the foregut, which consist of multipotent epithelial progenitors that organize into a complex tubular epithelial network. The trunk domain of each epithelial branch consists of bipotent pancreatic progenitors (bi-PPs) that give rise to both duct and endocrine lineages, whereas the tips give rise to acinar cells
1
. Here we identify the extrinsic and intrinsic signalling mechanisms that coordinate the fate-determining transcriptional events underlying these lineage decisions
1
,
2
. Single-cell analysis of pancreatic bipotent pancreatic progenitors derived from human embryonic stem cells reveal that cell confinement is a prerequisite for endocrine specification, whereas spreading drives the progenitors towards a ductal fate. Mechanistic studies identify the interaction of extracellular matrix (ECM) with integrin α5 as the extracellular cue that cell-autonomously, via the F-actin–YAP1–Notch mechanosignalling axis, controls the fate of bipotent pancreatic progenitors. Whereas ECM–integrin α5 signalling promotes differentiation towards the duct lineage, endocrinogenesis is stimulated when this signalling cascade is disrupted. This cascade can be disrupted pharmacologically or genetically to convert bipotent pancreatic progenitors derived from human embryonic stem cells to hormone-producing islet cells. Our findings identify the cell-extrinsic and intrinsic mechanotransduction pathway that acts as gatekeeper in the fate decisions of bipotent pancreatic progenitors in the developing pancreas.
Single-cell analysis reveals that interactions with the extracellular matrix via integrin α5 and mechanotransducer YAP1 determine whether pancreatic progenitors develop along the duct or endocrine lineages.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/31
/ 13/51
/ 13/95
/ 38
/ 38/77
/ 64/60
/ 96
/ 96/106
/ Actin
/ Adaptor Proteins, Signal Transducing - deficiency
/ Adaptor Proteins, Signal Transducing - genetics
/ Adaptor Proteins, Signal Transducing - metabolism
/ Animals
/ DNA-Binding Proteins - metabolism
/ Embryos
/ Enhancer Elements, Genetic - genetics
/ Explants
/ Female
/ Gene Expression Regulation, Developmental
/ Geometry
/ Hormones
/ Humanities and Social Sciences
/ Humans
/ Insulin
/ Integrin alpha5beta1 - metabolism
/ Kinases
/ Letter
/ Male
/ Mice
/ Muscle Proteins - metabolism
/ Pancreas
/ Phosphoproteins - deficiency
/ Phosphoproteins - metabolism
/ Science
/ Transcription Factor HES-1 - genetics
