美国加州大学Zev J. Gartner和Ophir D. Klein共同合作，近期取得重要工作进展。他们研究发现了活性间充质脱水作用对肠绒毛形成和折叠的影响。相关研究成果2024年5月22日在线发表于《细胞》杂志上。
据介绍，组织折叠是对器官功能至关重要的结构基序。在肠道中，扁平上皮弯曲成周期性的褶皱模式，产生绒毛，指状突起，使营养物质能够吸收。然而，驱动绒毛形态发生的分子和机械过程仍不清楚。
研究人员鉴定出一种主动的机械机制，它同时对肠上皮进行模式化和折叠，以启动绒毛的形成。在细胞水平上，研究人员发现PDGFRA+上皮下间充质细胞产生肌球蛋白II依赖性的力，足以在相邻组织界面产生图案曲率。这种对称性破坏过程需要改变细胞和细胞外基质的相互作用，这是由基质金属蛋白酶介导的组织流化所实现的。计算模型以及体外和体内实验表明，这些细胞特征在组织水平上表现为界面张力的差异，通过类似于薄液膜的主动去湿的过程促进间充质聚集和界面弯曲。
附：英文原文
Title: Patterning and folding of intestinal villi by active mesenchymal dewetting
Author: Tyler R. Huycke, Teemu J. Hkkinen, Hikaru Miyazaki, Vasudha Srivastava, Emilie Barruet, Christopher S. McGinnis, Ali Kalantari, Jake Cornwall-Scoones, Dedeepya Vaka, Qin Zhu, Hyunil Jo, Roger Oria, Valerie M. Weaver, William F. DeGrado, Matt Thomson, Krishna Garikipati, Dario Boffelli, Ophir D. Klein, Zev J. Gartner
Issue&Volume: 2024-05-22
Abstract: Tissue folds are structural motifs critical to organ function. In the intestine, bending of a flat epithelium into a periodic pattern of folds gives rise to villi, finger-like protrusions that enable nutrient absorption. However, the molecular and mechanical processes driving villus morphogenesis remain unclear. Here, we identify an active mechanical mechanism that simultaneously patterns and folds the intestinal epithelium to initiate villus formation. At the cellular level, we find that PDGFRA+ subepithelial mesenchymal cells generate myosin II-dependent forces sufficient to produce patterned curvature in neighboring tissue interfaces. This symmetry-breaking process requires altered cell and extracellular matrix interactions that are enabled by matrix metalloproteinase-mediated tissue fluidization. Computational models, together with in vitro and in vivo experiments, revealed that these cellular features manifest at the tissue level as differences in interfacial tensions that promote mesenchymal aggregation and interface bending through a process analogous to the active dewetting of a thin liquid film.
DOI: 10.1016/j.cell.2024.04.039
Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00465-3