Yin Lianhong, Gao Meng, Xu Lina, Qi Yan, Han Lan, Peng Jinyong
College of Pharmacy, Dalian Medical University, Dalian, Liaoning, 116044, China.
School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China.
J Pharm Anal. 2023 Jul;13(7):760-775. doi: 10.1016/j.jpha.2023.02.002. Epub 2023 Feb 7.
Nine major cell populations among 46,716 cells were identified in mouse intestinal ischemia‒reperfusion (II/R) injury by single-cell RNA sequencing. For enterocyte cells, 11 subclusters were found, in which enterocyte cluster 1 (EC1), enterocyte cluster 3 (EC3), and enterocyte cluster 8 (EC8) were newly discovered cells in ischemia 45 min/reperfusion 720 min (I 45 min/R 720 min) group. EC1 and EC3 played roles in digestion and absorption, and EC8 played a role in cell junctions. For TA cells, after ischemia 45 min/reperfusion 90 min (I 45 min/R 90 min), many TA cells at the stage of proliferation were identified. For Paneth cells, Paneth cluster 3 was observed in the resting state of normal jejunum. After I 45 min/R 90 min, three new subsets were found, in which Paneth cluster 1 had good antigen presentation activity. The main functions of goblet cells were to synthesize and secrete mucus, and a novel subcluster (goblet cluster 5) with highly proliferative ability was discovered in I 45 min/R 90 min group. As a major part of immune system, the changes in T cells with important roles were clarified. Notably, enterocyte cells secreted Guca2b to interact with Gucy2c receptor on the membranes of stem cells, TA cells, Paneth cells, and goblet cells to elicit intercellular communication. One marker known as glutathione S-transferase mu 3 (GSTM3) affected intestinal mucosal barrier function by adjusting mitogen-activated protein kinases (MAPK) signaling during II/R injury. The data on the heterogeneity of intestinal cells, cellular communication and the mechanism of GSTM3 provide a cellular basis for treating II/R injury.
通过单细胞RNA测序在小鼠肠道缺血再灌注（II/R）损伤的46716个细胞中鉴定出9个主要细胞群。对于肠上皮细胞，发现了11个亚群，其中肠上皮细胞簇1（EC1）、肠上皮细胞簇3（EC3）和肠上皮细胞簇8（EC8）是缺血45分钟/再灌注720分钟（I 45分钟/R 720分钟）组中的新发现细胞。EC1和EC3在消化和吸收中起作用，而EC8在细胞连接中起作用。对于TA细胞，在缺血45分钟/再灌注90分钟（I 45分钟/R 90分钟）后，鉴定出许多处于增殖阶段的TA细胞。对于潘氏细胞，在正常空肠的静止状态下观察到潘氏细胞簇3。在I 45分钟/R 90分钟后，发现了三个新的亚群，其中潘氏细胞簇1具有良好的抗原呈递活性。杯状细胞的主要功能是合成和分泌黏液，并且在I 45分钟/R 90分钟组中发现了一个具有高增殖能力的新亚群（杯状细胞簇5）。作为免疫系统的主要组成部分，明确了具有重要作用的T细胞的变化。值得注意的是，肠上皮细胞分泌Guca2b与干细胞、TA细胞、潘氏细胞和杯状细胞膜上的Gucy2c受体相互作用，引发细胞间通讯。一种名为谷胱甘肽S-转移酶μ3（GSTM3）的标志物在II/R损伤期间通过调节丝裂原活化蛋白激酶（MAPK）信号传导影响肠道黏膜屏障功能。肠道细胞异质性、细胞通讯以及GSTM3机制的数据为治疗II/R损伤提供了细胞基础。
