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人增殖期子宫内膜的基质异质性——一项单细胞RNA测序研究

Stromal Heterogeneity in the Human Proliferative Endometrium-A Single-Cell RNA Sequencing Study.

作者信息

Queckbörner Suzanna, von Grothusen Carolina, Boggavarapu Nageswara Rao, Francis Roy Mathew, Davies Lindsay C, Gemzell-Danielsson Kristina

机构信息

Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet, and Karolinska University Hospital, S-171 64 Solna, Sweden.

Department of Medical Biochemistry and Microbiology (IMBIM), Uppsala University, BMC, Husargatan 3, 752 37 Uppsala, Sweden.

出版信息

J Pers Med. 2021 May 22;11(6):448. doi: 10.3390/jpm11060448.

Abstract

The endometrium undergoes regular regeneration and stromal proliferation as part of the normal menstrual cycle. To better understand cellular interactions driving the mechanisms in endometrial regeneration we employed single-cell RNA sequencing. Endometrial biopsies were obtained during the proliferative phase of the menstrual cycle from healthy fertile women and processed to single-cell suspensions which were submitted for sequencing. In addition to known endometrial cell types, bioinformatic analysis revealed multiple stromal populations suggestive of specific stromal niches with the ability to control inflammation and extracellular matrix composition. Ten different stromal cells and two pericyte subsets were identified. Applying different R packages (Seurat, SingleR, Velocyto) we established cell cluster diversity and cell lineage/trajectory, while using external data to validate our findings. By understanding healthy regeneration in the described stromal compartments, we aim to identify points of further investigation and possible targets for novel therapy development for benign gynecological disorders affecting endometrial regeneration and proliferation such as endometriosis and Asherman's syndrome.

摘要

作为正常月经周期的一部分,子宫内膜会经历定期的再生和基质增殖。为了更好地理解驱动子宫内膜再生机制的细胞间相互作用,我们采用了单细胞RNA测序技术。在月经周期的增殖期,从健康的有生育能力的女性身上获取子宫内膜活检样本,并将其处理成单细胞悬液,然后送去进行测序。除了已知的子宫内膜细胞类型外,生物信息学分析还揭示了多个基质群体,提示存在特定的基质生态位,具有控制炎症和细胞外基质组成的能力。鉴定出了十种不同的基质细胞和两个周细胞亚群。应用不同的R包(Seurat、SingleR、Velocyto),我们建立了细胞簇多样性和细胞谱系/轨迹,同时利用外部数据验证我们的发现。通过了解上述基质区室中的健康再生情况,我们旨在确定进一步研究的要点以及针对影响子宫内膜再生和增殖的良性妇科疾病(如子宫内膜异位症和阿谢曼综合征)开发新疗法的可能靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef86/8224746/dc8225a9cbc6/jpm-11-00448-g001.jpg

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