A Specialized Niche in the Pancreatic Microenvironment Promotes Endocrine Differentiation.
A Specialized Niche in the Pancreatic Microenvironment Promotes Endocrine Differentiation.
复制标题
DOI:
10.1016/j.devcel.2020.08.003
复制
发表时间:
2020-10-26
影响因子:
11.8
通讯作者:
Spagnoli FM
中科院分区:
文献类型:
--
作者:
Cozzitorto C;Mueller L;Ruzittu S;Mah N;Willnow D;Darrigrand JF;Wilson H;Khosravinia D;Mahmoud AA;Risolino M;Selleri L;Spagnoli FM
The interplay between pancreatic epithelium and surrounding microenvironment is pivotal for pancreas formation and differentiation as well as adult organ homeostasis. The mesenchyme is the main component of the embryonic pancreatic microenvironment, yet its cellular identity is broadly defined and whether it comprises functionally distinct cell subsets is not known. Using genetic lineage tracing, transcriptome and functional studies, we identified mesenchymal populations with different roles during pancreatic development. Moreover, we showed that Pbx transcription factors act within the mouse pancreatic mesenchyme to define a pro-endocrine specialized niche. Pbx directs differentiation of endocrine progenitors into insulin- and glucagon-positive cells through non-cell-autonomous regulation of ECM-integrin interactions and soluble molecules. Next, we measured functional conservation between mouse and human pancreatic mesenchyme by testing identified mesenchymal factors in an iPSC-based differentiation model. Our findings provide insights into how lineage-specific crosstalk between epithelium and neighboring mesenchymal cells underpin the generation of different pancreatic cell types. The diversity of mesenchymal cell types in the pancreas that influence cell differentiation is poorly defined. Cozzitorto et al. identified a specialized microenvironment that surrounds the developing pancreas and promotes the formation of insulin-producing cells.
登录
查看更多内容
影响因子:
16.6
作者:
Byrnes LE;Wong DM;Subramaniam M;Meyer NP;Gilchrist CL;Knox SM;Tward AD;Ye CJ;Sneddon JB
通讯作者:
Sneddon JB
影响因子:
2.7
作者:
Harari, Neta;Sakhneny, Lina;Khalifa-Malka, Laura;Busch, Anke;Hertel, Klemens J.;Hebrok, Matthias;Landsman, Limor
通讯作者:
Landsman, Limor
影响因子:
30.8
作者:
Kim, SK;Selleri, L;Cleary, ML
通讯作者:
Cleary, ML
影响因子:
50.3
作者:
Hingorani, SR;Petricoin, EF;Tuveson, DA
通讯作者:
Tuveson, DA
影响因子:
10.5
作者:
Asayesh, Amir;Sharpe, James;Ahlgren, Ulf
通讯作者:
Ahlgren, Ulf