Zhao Yu, Zhou Ran, Xie Bingqing, Liu Cambrian Y, Kalski Martin, Cham Candace M, Jiang Zhiwei, Koval Jason, Weber Christopher R, Rubin David T, Sogin Mitch, Crosson Sean, Chen Mengjie, Huang Jun, Fiebig Aretha, Dalal Sushila, Chang Eugene B, Basu Anindita, Pott Sebastian
University of Chicago, Pritzker School of Molecular Engineering, Chicago, IL, USA.
University of Chicago, Department of Medicine, Chicago, IL, USA.
medRxiv. 2025 Jan 9:2023.11.11.23298309. doi: 10.1101/2023.11.11.23298309.
Total proctocolectomy with ileal pouch anal anastomosis is the standard of care for patients with severe ulcerative colitis. We generated a cell-type-resolved transcriptional and epigenetic atlas of ileal pouches using scRNA-seq and scATAC-seq data from paired biopsy samples of the ileal pouch and the ileal segment above the pouch (pre-pouch) from patients (male=4, female=2), and paired biopsies of the terminal ileum and ascending colon from healthy individuals (male=3, female=3) serving as reference. Our study finds previously uncharacterized populations of absorptive and secretory epithelial cells within the pouch but not the pre-pouch. These pouch-specific enterocytes express a subset of colon-specific genes, including and . However, compared to normal colonocytes, expression of these genes is lower, and these enterocytes also express inflammatory and secretory genes while maintaining expression of some ileal-specific genes. This cell-type-resolved transcriptomic and epigenetic atlas of the ileal pouch establishes a reference for investigating pouch physiology and pathology.
全直肠结肠切除术加回肠贮袋肛管吻合术是重症溃疡性结肠炎患者的标准治疗方法。我们使用来自患者（男性 = 4，女性 = 2）回肠贮袋及贮袋上方回肠段（贮袋前）的配对活检样本的scRNA-seq和scATAC-seq数据，以及来自健康个体（男性 = 3，女性 = 3）的终末回肠和升结肠的配对活检样本作为参考，生成了回肠贮袋的细胞类型解析转录组和表观基因组图谱。我们的研究发现贮袋内存在先前未被表征的吸收性和分泌性上皮细胞群体，但贮袋前不存在。这些贮袋特异性肠上皮细胞表达一组结肠特异性基因的子集，包括 和 。然而，与正常结肠细胞相比，这些基因的表达较低，并且这些肠上皮细胞在维持一些回肠特异性基因表达的同时还表达炎症和分泌基因。这个回肠贮袋的细胞类型解析转录组和表观基因组图谱为研究贮袋生理学和病理学建立了一个参考。
