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

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. DinhAmal EL-Naggar, David G. Huntsman, Michael S. Anglesio, Marc T. Goodman, Fabiola Medeiros, Matthew Siedhoff, Kate Lawrenson

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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.

Original language	English (US)
Pages (from-to)	255-267
Number of pages	13
Journal	Nature Genetics
Volume	55
Issue number	2
DOIs	https://doi.org/10.1038/s41588-022-01254-1
State	Published - Feb 2023
Externally published	Yes

ASJC Scopus subject areas

Genetics

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Fonseca, M. A. S., Haro, M., Wright, K. N., Lin, X., Abbasi, F., Sun, J., Hernandez, L., Orr, N. L., Hong, J., Choi-Kuaea, Y., Maluf, H. M., Balzer, B. L., Fishburn, A., Hickey, R., Cass, I., Goodridge, H. S., Truong, M., Wang, Y., Pisarska, M. D., ... Lawrenson, K. (2023). Single-cell transcriptomic analysis of endometriosis. Nature Genetics, 55(2), 255-267. https://doi.org/10.1038/s41588-022-01254-1

Fonseca, MAS, Haro, M, Wright, KN, Lin, X, Abbasi, F, Sun, J, Hernandez, L, Orr, NL, Hong, J, Choi-Kuaea, Y, Maluf, HM, Balzer, BL, Fishburn, A, Hickey, R, Cass, I, Goodridge, HS, Truong, M, Wang, Y, Pisarska, MD, Dinh, HQ, EL-Naggar, A, Huntsman, DG, Anglesio, MS, Goodman, MT, Medeiros, F, Siedhoff, M & Lawrenson, K 2023, 'Single-cell transcriptomic analysis of endometriosis', Nature Genetics, vol. 55, no. 2, pp. 255-267. https://doi.org/10.1038/s41588-022-01254-1

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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.",

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

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AU - Fonseca, Marcos A.S.

AU - Haro, Marcela

AU - Wright, Kelly N.

AU - Lin, Xianzhi

AU - Abbasi, Forough

AU - Sun, Jennifer

AU - Hernandez, Lourdes

AU - Orr, Natasha L.

AU - Hong, Jooyoon

AU - Choi-Kuaea, Yunhee

AU - Maluf, Horacio M.

AU - Balzer, Bonnie L.

AU - Fishburn, Aaron

AU - Hickey, Ryan

AU - Cass, Ilana

AU - Goodridge, Helen S.

AU - Truong, Mireille

AU - Wang, Yemin

AU - Pisarska, Margareta D.

AU - Dinh, Huy Q.

AU - EL-Naggar, Amal

AU - Huntsman, David G.

AU - Anglesio, Michael S.

AU - Goodman, Marc T.

AU - Medeiros, Fabiola

AU - Siedhoff, Matthew

AU - Lawrenson, Kate

PY - 2023/2

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N2 - 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.

AB - 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.

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Single-cell transcriptomic analysis of endometriosis

Abstract

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