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Int J Biol Sci 2023; 19(8):2515-2530. doi:10.7150/ijbs.83510 This issue Cite

Research Paper

Integrating Spatial Transcriptomics and Single-nucleus RNA Sequencing Reveals the Potential Therapeutic Strategies for Uterine Leiomyoma

Jianzhang Wang^1,2*, Ping Xu^1*, Gen Zou^1*, Xuan Che^3*, Xiaohong Jiang³, Yuanmeng Liu¹, Xinqi Mao¹, Xinmei Zhang^1,2✉

1. Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China, 310006.
2. Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China, 310006.
3. Department of Gynecology, Jiaxing University Affiliated Women and Children Hospital, Jiaxing, Zhejiang, P.R. China, 314000.
^* These authors contributed equally to this work.

✉ Corresponding author: Xinmei Zhang, MD, PhD, Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Hangzhou, Zhejiang, P.R. China, 310006. Phone: 86-571-87061501-2131; Fax: 86-571-87061878; E-mail: zhangxinmedu.cn. More

Abstract

Uterine leiomyoma is the most common gynecological tumor in reproductive women. Tumor-host interface is a complex ecosystem with intimate cell-cell communications and a critical scenario for tumor pathogenesis and progression. The pseudocapsule is the main tumor-host interface of uterine leiomyoma, but its cellular spatial disposition and gene expression are poorly explored. This study mapped the cellular architecture and corresponding gene profiles of the leiomyoma and its surrounding pseudocapsule by integrating spatial transcriptomics and single-nucleus RNA-sequencing at the first time. Here, we reported that estrogen receptor alpha and progesterone receptor mediated the occurrence and development of uterine leiomyoma and that estrogen receptor beta involved in the angiogenesis, which explained the effectiveness of hormonotherapy. Therapeutic targets including ERK1/ERK2 pathway and IGF1-IGF1R were found and might be applied for non-hormonal therapy of uterine leiomyoma. Furthermore, the injection of prostaglandin E2 was initially presented for bleeding control during myomectomy, injection site should be located at the junction between pseudocapsule and leiomyoma, and surrounding pseudocapsule should not be eliminated. Collectively, a single-cell and spatially resolved atlas of human uterine leiomyoma and its surrounding pseudocapsule was established. The results revealed potentially feasible strategies for hormonotherapy, non-hormonal targeted therapy and bleeding control during myomectomy.

Keywords: Uterine leiomyoma, Pseudocapsule, Spatial transcriptomics, Single-cell RNA sequencing, Bleeding control, prostaglandin E2

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