Leucine-rich repeat–containing G-protein–coupled receptor 5–positive cells in the endometrial stem cell niche

Leucine-rich repeat–containing G-protein–coupled receptor 5 (LGR5) is not an endogenous stem cell marker for human endometrium, but LGR5-positive cells contribute to the endometrial stem cell niche.

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Volume 107, Issue 2, Pages 510–519

Authors:

Irene Cervelló, Ph.D., Claudia Gil-Sanchis, Ph.D., Xavier Santamaría, Ph.D., M.D., Amparo Faus, B.Sc., Julia Vallvé-Juanico, Ph.D., Patricia Díaz-Gimeno, Ph.D., Oriana Genolet, Ph.D., Antonio Pellicer, Ph.D., M.D., Carlos Simón, Ph.D., M.D.

Abstract:

Objective

To study, isolate and characterize leucine-rich repeat–containing heterotrimeric guanine nucleotide–binding protein–coupled receptor 5 (LGR5)–positive cells from human endometrium to determine their functional relevance.

Design

Prospective experimental animal study.

Setting

University research laboratories.

Animal(s)

Nonobese diabetic mice (NOD-SCID) (strain code 394; NOD.CB17—Prkdcscid/NcrCrl).

Intervention(s)

Human LGR5+ cells were labeled with superparamagnetic iron oxide nanoparticles (SPIOs) and injected under the kidney capsule in immunocompromised mice.

Main Outcome Measure(s)

Epithelial and stromal LGR5+ cells were isolated from human endometrium by means of fluorescence-activated cell sorting, and phenotypic characterization was performed by means of flow cytometry with the use of hematopoietic and mesenchymal markers. Engrafted SPIO-labeled LGR5+ cells were localized with the use of Prussian blue staining and immunohistochemistry against CD9 and Vimentin. Deep transcriptomic profiling of LGR5+ cells was performed with the use of microarrays and RNA sequencing.

Result(s)

The percentage of LGR5+ cells in human endometrium represented 1.08 ± 0.73% and 0.82 ± 0.76% of total cells in the epithelial and stromal compartments, respectively. LGR5+ cells were phenotypically characterized by abundant expression of CD45 hematopoietic marker and no expression of surface markers CD31, CD34, CD133, CD73, and CD90. Coexpression with the macrophage marker CD163 was detected. Xenotransplantation of labeled LGR5+ cells into the kidney capsules of immunocompromised mice resulted in a weak endometrial reconstitution from this cell of origin. Transcriptomic profiling revealed new attributes for LGR5+ cells related to their putative hematopoietic origin.

Conclusion(s)

These data suggest that endometrial LGR5 is not an endogenous stem cell marker. Instead, LGR5+ cells appear to be recruited from blood to be part of the stem cell niche at the perivascular microenvironment to activate the endogenous niche.


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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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