Single-cell transcriptomic analysis of endometriosis

Marcos A S Fonseca; Marcela Haro; Kelly N Wright; Xianzhi Lin; Forough Abbasi; Jennifer Sun; Lourdes Hernandez; Natasha L Orr; Jooyoon Hong; Yunhee Choi-Kuaea; Horacio M Maluf; Bonnie L Balzer; Aaron Fishburn; Ryan Hickey; Ilana Cass; Helen S Goodridge; Mireille Truong; Yemin Wang; Margareta D Pisarska; Huy Q Dinh; Amal El-Naggar; David G Huntsman; Michael S Anglesio; Marc T Goodman; Fabiola Medeiros; Matthew Siedhoff; Kate Lawrenson

doi:10.1038/s41588-022-01254-1

Single-cell transcriptomic analysis of endometriosis

Nat Genet. 2023 Feb;55(2):255-267. doi: 10.1038/s41588-022-01254-1. Epub 2023 Jan 9.

Authors

Marcos A S Fonseca^#^{1

2}, Marcela Haro^#^{1

2}, Kelly N Wright^#³, Xianzhi Lin^#^{1

2}, Forough Abbasi^{1

2}, Jennifer Sun^{1

2}, Lourdes Hernandez^{1

2}, Natasha L Orr⁴, Jooyoon Hong⁴, Yunhee Choi-Kuaea⁵, Horacio M Maluf⁶, Bonnie L Balzer⁶, Aaron Fishburn⁶, Ryan Hickey⁶, Ilana Cass^{2

7}, Helen S Goodridge^{8

9}, Mireille Truong³, Yemin Wang^{4

10}, Margareta D Pisarska^{11

12}, Huy Q Dinh^{13

14}, Amal El-Naggar^{8

15}, David G Huntsman^{4

10}, Michael S Anglesio^{4

16}, Marc T Goodman⁵, Fabiola Medeiros⁶, Matthew Siedhoff³, Kate Lawrenson^{17

18

19

20}

Affiliations

¹ Women's Cancer Research Program at the Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
² Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
³ Division of Minimally Invasive Gynecologic Surgery, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁴ Department of Obstetrics and Gynecology, UBC, Vancouver, British Columbia, Canada.
⁵ Cancer Prevention and Control Program, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁶ Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁷ Department of Obstetrics and Gynecology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
⁸ Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁹ Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
¹⁰ Department of Pathology and Laboratory Medicine, University of British Columbia, and Department of Molecular Oncology, British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada.
¹¹ Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
¹² Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
¹³ McArdle Laboratory for Cancer Research, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
¹⁴ Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
¹⁵ Department of Pathology, Faculty of Medicine, Menoufia University, Menoufia Governorate, Egypt.
¹⁶ British Columbia's Gynecological Cancer Research (OVCARE) Program, University of British Columbia, Vancouver General Hospital, and BC Cancer, Vancouver, British Columbia, Canada.
¹⁷ Women's Cancer Research Program at the Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA. [email protected].
¹⁸ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. [email protected].
¹⁹ Cancer Prevention and Control Program, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA. [email protected].
²⁰ Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA. [email protected].

^# Contributed equally.

Abstract

Endometriosis is a common condition in women that causes chronic pain and infertility and is associated with an elevated risk of ovarian cancer. We profiled transcriptomes of >370,000 individual cells from endometriomas (n = 8), endometriosis (n = 28), eutopic endometrium (n = 10), unaffected ovary (n = 4) and endometriosis-free peritoneum (n = 4), generating a cellular atlas of endometrial-type epithelial cells, stromal cells and microenvironmental cell populations across tissue sites. Cellular and molecular signatures of endometrial-type epithelium and stroma differed across tissue types, suggesting a role for cellular restructuring and transcriptional reprogramming in the disease. Epithelium, stroma and proximal mesothelial cells of endometriomas showed dysregulation of pro-inflammatory pathways and upregulation of complement proteins. Somatic ARID1A mutation in epithelial cells was associated with upregulation of pro-angiogenic and pro-lymphangiogenic factors and remodeling of the endothelial cell compartment, with enrichment of lymphatic endothelial cells. Finally, signatures of ciliated epithelial cells were enriched in ovarian cancers, reinforcing epidemiologic associations between these two diseases.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Endometriosis* / genetics
Endometriosis* / metabolism
Endothelial Cells / metabolism
Epithelial Cells / metabolism
Epithelium
Female
Humans
Transcriptome* / genetics

Abstract

Publication types

MeSH terms

Grants and funding