title: Leucine-rich repeat-containing G-protein-coupled receptor 5-positive cells in the endometrial stem cell niche.
abstract: 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.
  
  
  
  Prospective experimental animal study.
  
  
  
  University research laboratories.
  
  
  
  Nonobese diabetic mice (NOD-SCID) (strain code 394; NOD.CB17-Prkdcscid/NcrCrl).
  
  
  
  Human LGR5+cells were labeled with superparamagnetic iron oxide nanoparticles (SPIOs) and injected under the kidney capsule in immunocompromised mice.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Fundación Instituto Valenciano de Infertilidad, Department of Obstetrics and Gynecology, School of Medicine, Valencia University and Instituto Universitario IVI/INCLIVA, Valencia, Spain. Electronic address: irene.cervello@ivi.es.
authors.forename: Irene
authors.initials: I
authors.lastname: Cervelló
authors.affiliation: Fundación Instituto Valenciano de Infertilidad, Department of Obstetrics and Gynecology, School of Medicine, Valencia University and Instituto Universitario IVI/INCLIVA, Valencia, Spain.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gil-Sanchis
authors.affiliation: Fundación Instituto Valenciano de Infertilidad, Department of Obstetrics and Gynecology, School of Medicine, Valencia University and Instituto Universitario IVI/INCLIVA, Valencia, Spain; IVI Barcelona, Reproductive Medicine Department, Barcelona, Spain; Vall Hebron Institut de Recerca, Biomedical Research Group in Gynecology, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Santamaría
authors.affiliation: Fundación Instituto Valenciano de Infertilidad, Department of Obstetrics and Gynecology, School of Medicine, Valencia University and Instituto Universitario IVI/INCLIVA, Valencia, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Faus
authors.affiliation: IVI Barcelona, Reproductive Medicine Department, Barcelona, Spain; Vall Hebron Institut de Recerca, Biomedical Research Group in Gynecology, Barcelona, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Vallvé-Juanico
authors.affiliation: Fundación Instituto Valenciano de Infertilidad, Department of Obstetrics and Gynecology, School of Medicine, Valencia University and Instituto Universitario IVI/INCLIVA, Valencia, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Díaz-Gimeno
authors.affiliation: Fundación Instituto Valenciano de Infertilidad, Department of Obstetrics and Gynecology, School of Medicine, Valencia University and Instituto Universitario IVI/INCLIVA, Valencia, Spain.
authors.forename: Oriana
authors.initials: O
authors.lastname: Genolet
authors.affiliation: Fundación Instituto Valenciano de Infertilidad, Department of Obstetrics and Gynecology, School of Medicine, Valencia University and Instituto Universitario IVI/INCLIVA, Valencia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pellicer
authors.affiliation: Fundación Instituto Valenciano de Infertilidad, Department of Obstetrics and Gynecology, School of Medicine, Valencia University and Instituto Universitario IVI/INCLIVA, Valencia, Spain; Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford University, Stanford, California.
authors.forename: Carlos
authors.initials: C
authors.lastname: Simón
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D004717:Endometrium / Q000378:metabolism* / Q000637:transplantation; D004847:Epithelial Cells / Q000378:metabolism* / Q000637:transplantation; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D064593:Heterografts; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000601:surgery; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010641:Phenotype; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D055153:Stem Cell Niche; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism* / Q000637:transplantation; D059467:Transcriptome
chemical_list: D015415:Biomarkers; C116884:LGR5 protein, human; D043562:Receptors, G-Protein-Coupled
keywords: LGR5; Somatic stem cells; hematopoietic lineage; human endometrium; stem cell marker