Edri Shlomit, Rosenthal Vardit, Ginsburg Or, Newman Frisch Abigail, Pierreux Christophe E, Sharon Nadav, Levenberg Shulamit
Faculty of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa 3200003, Israel.
Cell Biology Unit, de Duve Institute, UCLouvain, Woluwe, 1200 Brussels, Belgium.
iScience. 2024 May 10;27(6):109959. doi: 10.1016/j.isci.2024.109959. eCollection 2024 Jun 21.
The developing mouse pancreas is surrounded by mesoderm compartments providing signals that induce pancreas formation. Most pancreatic organoid protocols lack this mesoderm niche and only partially capture the pancreatic cell repertoire. This work aims to generate pancreatic aggregates by differentiating mouse embryonic stem cells (mESCs) into mesoderm progenitors (MPs) and pancreas progenitors (PPs), without using Matrigel. First, mESCs were differentiated into epiblast stem cells (EpiSCs) to enhance the PP differentiation rate. Next, PPs and MPs aggregated together giving rise to various pancreatic cell types, including endocrine, acinar, and ductal cells, and to endothelial cells. Single-cell RNA sequencing analysis revealed a larger endocrine population within the PP + MP aggregates, as compared to PPs alone or PPs in Matrigel aggregates. The PP + MP aggregate gene expression signatures and its endocrine population percentage closely resembled those of the endocrine population found in the mouse embryonic pancreas, which holds promise for studying pancreas development.
发育中的小鼠胰腺被中胚层隔室包围，这些隔室提供诱导胰腺形成的信号。大多数胰腺类器官培养方案缺乏这种中胚层生态位，只能部分捕获胰腺细胞库。这项工作旨在通过将小鼠胚胎干细胞（mESCs）分化为中胚层祖细胞（MPs）和胰腺祖细胞（PPs）来生成胰腺聚集体，而不使用基质胶。首先，将mESCs分化为上胚层干细胞（EpiSCs）以提高PP的分化率。接下来，PPs和MPs聚集在一起，产生了各种胰腺细胞类型，包括内分泌细胞、腺泡细胞和导管细胞，以及内皮细胞。单细胞RNA测序分析显示，与单独的PPs或基质胶聚集体中的PPs相比，PP + MP聚集体中的内分泌细胞群体更大。PP + MP聚集体的基因表达特征及其内分泌细胞群体百分比与小鼠胚胎胰腺中的内分泌细胞群体非常相似，这为研究胰腺发育带来了希望。
