通过整合组学解码组织驻留子宫树突状细胞的功能和发育轨迹

Decoding Functional and Developmental Trajectories of Tissue-Resident Uterine Dendritic Cells Through Integrative Omics.

作者信息

Mor Gil, Singh Aditi, Yang Jing, Adzibolosu Nicholas, Cai Songchen, Kauf Elana, Yang Lingtao, Li Qiyuan, Li Hanjie, Werner Alexandra, Parthasarathy Siddharth, Ding Jiahui, Fortier Jared, Rodriguez-Garcia Marta, Diao Liang-Hui

机构信息

Wayne State University.

National Institute for Data Science in Health and Medicine, School of Medicine, Xiamen University, Xiamen 361102, China.

出版信息

Res Sq. 2024 Nov 14:rs.3.rs-5424920. doi: 10.21203/rs.3.rs-5424920/v1.

Abstract

Uterine dendritic cells (uDCs) are critical for endometrial function, yet their origin, molecular characteristics, and specific roles during the pre- and post-implantation periods in the human endometrium remain largely unknown. The complexity of the endometrial environment makes defining the contributions of uDCs subtypes challenging. We hypothesize that distinct uDC subsets carry out specialized functions, and that resident progenitor DCs generate these subtypes. Employing single-cell RNA sequencing on uterine tissues collected across different menstrual phases and during early pregnancy, we identify several uDCs subtypes, including resident progenitor DCs. CITE-seq was performed on endometrial single-cell suspensions to link surface protein expression with key genes identified by the RNAseq analysis. Our analysis revealed the developmental trajectory of the uDCs along with the distinct functional roles of each uDC subtype, including immune regulation, antigen presentation, and creating a conducive environment for embryo implantation. This study provides a comprehensive characterization of uDCs, serving as a foundational reference for future studies for better understanding female reproductive disorders such as infertility and pregnancy complications.

摘要

子宫树突状细胞(uDCs)对子宫内膜功能至关重要,但其起源、分子特征以及在人类子宫内膜植入前和植入后时期的具体作用仍在很大程度上未知。子宫内膜环境的复杂性使得确定uDCs亚型的贡献具有挑战性。我们假设不同的uDC亚群执行专门的功能,并且驻留祖细胞DC产生这些亚型。通过对在不同月经周期阶段和妊娠早期收集的子宫组织进行单细胞RNA测序,我们鉴定出几种uDCs亚型,包括驻留祖细胞DC。对子宫内膜单细胞悬液进行细胞索引转录组测序(CITE-seq),以将表面蛋白表达与RNA测序分析鉴定的关键基因联系起来。我们的分析揭示了uDCs的发育轨迹以及每个uDC亚型的不同功能作用,包括免疫调节、抗原呈递以及为胚胎植入创造有利环境。这项研究提供了uDCs的全面特征,为未来更好地理解诸如不孕症和妊娠并发症等女性生殖疾病的研究奠定了基础参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb01/11601813/ee20c437e4bf/nihpp-rs5424920v1-f0001.jpg

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