Single-cell transcriptomic analysis of endometriosis

被引：84

作者：

Fonseca, Marcos A. S. ^{[1
,2
]}

Haro, Marcela ^{[1
,2
]}

Wright, Kelly N. ^{[3
]}

Lin, Xianzhi ^{[1
,2
]}

Abbasi, Forough ^{[1
,2
]}

Sun, Jennifer ^{[1
,2
]}

Hernandez, Lourdes ^{[1
,2
]}

Orr, Natasha L. ^{[4
]}

Hong, Jooyoon ^{[4
]}

Choi-Kuaea, Yunhee ^{[5
]}

Maluf, Horacio M. ^{[6
]}

Balzer, Bonnie L. ^{[6
]}

Fishburn, Aaron ^{[6
]}

Hickey, Ryan ^{[6
]}

Cass, Ilana ^{[2
]}

Goodridge, Helen S. ^{[7
,8
]}

Truong, Mireille ^{[3
]}

Wang, Yemin ^{[4
,9
]}

Pisarska, Margareta D. ^{[10
,11
]}

Dinh, Huy Q. ^{[12
,13
]}

EL-Naggar, Amal ^{[7
,14
]}

Huntsman, David G. ^{[4
,9
]}

Anglesio, Michael S. ^{[4
,15
,16
]}

Goodman, Marc T. ^{[5
]}

Medeiros, Fabiola ^{[6
]}

Siedhoff, Matthew ^{[3
]}

Lawrenson, Kate ^{[1
,2
,5
,17
]}

机构：

[1] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Ctr, Womens Canc Res Program, Los Angeles, CA 90048 USA

[2] Cedars Sinai Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Los Angeles, CA 90048 USA

[3] Cedars Sinai Med Ctr, Dept Obstet & Gynecol, Div Minimally Invas Gynecol Surg, Los Angeles, CA USA

[4] Univ British Columbia, Dept Obstet & Gynecol, Vancouver, BC, Canada

[5] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Ctr, Canc Prevent & Control Program, Los Angeles, CA 90048 USA

[6] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA USA

[7] Cedars Sinai Med Ctr, Board Governors Regenerat Med Inst, Los Angeles, CA USA

[8] Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA USA

[9] Univ British Columbia, British Columbia Canc Res Inst, Dept Pathol & Lab Med, Vancouver, BC, Canada

[10] Dartmouth Hitchcock Med Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Lebanon, NH USA

[11] UCLA, Dept Obstet & Gynecol, David Geffen Sch Med, Los Angeles, CA USA

[12] Univ Wisconsin, Madison Sch Med & Publ Hlth, McArdle Lab Canc Res, Madison, WI USA

[13] Univ Wisconsin, Madison Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI USA

[14] Menoufia Univ, Fac Med, Dept Pathol, Menoufia Governorate, Egypt

[15] Univ British Columbia, Vancouver Gen Hosp, British Columbias Gynecol Canc Res OVCARE Program, Vancouver, BC, Canada

[16] Univ British Columbia, BC Canc, Vancouver, BC, Canada

[17] Cedars Sinai Med Ctr, Ctr Bioinformat & Funct Genom, Los Angeles, CA 90048 USA

来源：

NATURE GENETICS | 2023年 / 55卷 / 02期

基金：

美国国家卫生研究院; 加拿大健康研究院;

关键词：

D O I：

10.1038/s41588-022-01254-1

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：255 / 267

页数：13

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