Single-cell and spatial mapping Identify cell types and signaling Networks in the human ureter.
Single-cell and spatial mapping Identify cell types and signaling Networks in the human ureter.
复制标题
DOI：
10.1016/j.devcel.2022.07.004
复制
发表时间：
2022-08-08
影响因子：
11.8
通讯作者：
Ting, Angela H.
中科院分区：
文献类型：
--
作者：
Fink, Emily E.;Sona, Surbhi;Tran, Uyen;Desprez, Pierre-Emmanuel;Bradley, Matthew;Qiu, Hong;Eltemamy, Mohamed;Wee, Alvin;Wolkov, Madison;Nicolas, Marlo;Min, Booki;Haber, Georges-Pascal;Wessely, Oliver;Lee, Byron H.;Ting, Angela H.
组织工程为输尿管狭窄提供了一种有前途的治疗策略，但其成功需要深入了解组织再生的结构，细胞异质性和信号通路。在这里，我们使用单细胞RNA测序、空间基因表达和免疫荧光方法来定义和空间映射人类输尿管内的细胞群。我们专注于间质和尿路上皮细胞群，列举不同的细胞类型组成的人输尿管和推断潜在的细胞间通讯网络支持这些隔间之间的双向串扰。此外，我们分析和实验验证的Sonic Hedgehog（SHH）信号通路在成体祖细胞的维护的重要性。表达SHH的基底细胞支持体外类器官生成，并准确预测从基底祖细胞到终末分化的伞细胞的分化轨迹。我们的研究结果突出了成人输尿管组织稳态的基本过程，并为指导输尿管组织工程提供了蓝图。Fink和索纳等人详细描述了人输尿管的细胞组成和组织，鉴定了以前未被认识到的免疫丰富性、尿路上皮周成纤维细胞和基底细胞之间的串扰以及表达SHH的成人尿路上皮祖细胞。这些观察将有助于了解人类输尿管的再生潜力
Tissue engineering offers a promising treatment strategy for ureteral strictures, but its success requires an in-depth understanding of the architecture, cellular heterogeneity, and signaling pathways underlying tissue regeneration. Here we define and spatially map cell populations within the human ureter using single-cell RNA sequencing, spatial gene expression, and immunofluorescence approaches. We focus on the stromal and urothelial cell populations to enumerate distinct cell types composing the human ureter and infer potential cell-cell communication networks underpinning the bi-directional crosstalk between these compartments. Furthermore, we analyze and experimentally validate the importance of Sonic Hedgehog (SHH) signaling pathway in adult progenitor cell maintenance. The SHH-expressing basal cells support organoid generation in vitro and accurately predict the differentiation trajectory from basal progenitor cells to terminally differentiated umbrella cells. Our results highlight essential processes involved in adult ureter tissue homeostasis and provide a blueprint for guiding ureter tissue engineering. Fink and Sona et al. present a detailed description of the cellular composition and organization of the human ureter, identifying previously unappreciated immune richness, crosstalk between periurothelial fibroblast and basal cells, and adult SHH-expressing urothelial progenitor cells. These observations will help understand the regenerative potential in the human ureter
登录
查看更多内容
影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
2.6
作者：
Gild P;Kluth LA;Vetterlein MW;Engel O;Chun FKH;Fisch M
通讯作者：
Fisch M
单细胞 RNA 测序强调了炎性癌症相关成纤维细胞在膀胱尿路上皮癌中的作用。
影响因子：
16.6
作者：
Chen Z;Zhou L;Liu L;Hou Y;Xiong M;Yang Y;Hu J;Chen K
通讯作者：
Chen K
影响因子：
13.3
作者：
Bauckman, Kyle A.;Mysorekar, Indira U.
通讯作者：
Mysorekar, Indira U.
影响因子：
16.2
作者：
Armand EJ;Li J;Xie F;Luo C;Mukamel EA
通讯作者：
Mukamel EA