Differentiating mouse embryonic stem cells express markers of human endometrium

Reproductive Biology and Endocrinology

Research

P. Parasar¹  R. M. Anchan¹  M. R. Laufer²  S. A. Missmer³  S. Salas⁴  E. R. McGuirk⁴  C. R. Sacha⁴  N. Ng⁴  P. Ozcan⁴  J. Lindsey⁴  S. Chinthala⁵ 

[1] Boston Center for Endometriosis, Boston Children’s and Brigham and Women’s Hospitals, 333 and 221 Longwood Avenue, 02115, Boston, MA, USA;Center for Infertility and Reproductive Surgery, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women’s Hospital and Harvard Medical School, 75 Francis Street, 02115, Boston, MA, USA;Boston Center for Endometriosis, Boston Children’s and Brigham and Women’s Hospitals, 333 and 221 Longwood Avenue, 02115, Boston, MA, USA;Center for Infertility and Reproductive Surgery, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women’s Hospital and Harvard Medical School, 75 Francis Street, 02115, Boston, MA, USA;Division of Gynecology, Department of Surgery, Boston Children’s Hospital, 300 Longwood Avenue, 02115, Boston, MA, USA;Boston Center for Endometriosis, Boston Children’s and Brigham and Women’s Hospitals, 333 and 221 Longwood Avenue, 02115, Boston, MA, USA;Division of Adolescent and Young Adult Medicine, Department of Medicine, Boston Children’s Hospital and Harvard Medical School, 300 Longwood Avenue, 02115, Boston, MA, USA;Department of Epidemiology, Harvard T. H. Chan School of Public Health, 677 Huntington Ave, 02115, Boston, MA, USA;Center for Infertility and Reproductive Surgery, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women’s Hospital and Harvard Medical School, 75 Francis Street, 02115, Boston, MA, USA;Center for Infertility and Reproductive Surgery, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women’s Hospital and Harvard Medical School, 75 Francis Street, 02115, Boston, MA, USA;Department of OB/GYN, University of Chicago, 5841 S. Maryland Ave, 60637, Chicago, IL, USA;

关键词: Mouse embryonic stem cells;    Endometrium;    Differentiation;    Animal model;    Endometriosis;   

DOI  :  10.1186/s12958-017-0273-2

 received in 2017-03-10, accepted in 2017-07-06,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundModeling early endometrial differentiation is a crucial step towards understanding the divergent pathways between normal and ectopic endometrial development as seen in endometriosis.MethodsTo investigate these pathways, mouse embryonic stem cells (mESCs) and embryoid bodies (EBs) were differentiated in standard EB medium (EBM). Immunofluorescence (IF) staining and reverse-transcription polymerase chain reaction (RT-PCR) were used to detect expression of human endometrial cell markers on differentiating cells, which were sorted into distinct populations using fluorescence-activated cell sorting (FACS).ResultsA subpopulation (50%) of early differentiating mESCs expressed both glandular (CD9) and stromal (CD13) markers of human endometrium, suggestive of a novel endometrial precursor cell population. We further isolated a small population of endometrial mesenchymal stem cells, CD45−/CD146+/PDGFR-β+, from differentiating EBs, representing 0.7% of total cells. Finally, quantitative PCR demonstrated significantly amplified expression of transcription factors Hoxa10 and Foxa2 in CD13+ EBs isolated by FACS (p = 0.03).ConclusionsThese findings demonstrate that mESCs have the capacity to express human endometrial cell markers and demonstrate potential differentiation pathways of endometrial precursor and mesenchymal stem cells, providing an in vitro system to model early endometrial tissue development. This model represents a key step in elucidating the mechanisms of ectopic endometrial tissue growth. Such a system could enable the development of strategies to prevent endometriosis and identify approaches for non-invasive monitoring of disease progression.

【 授权许可】

CC BY   
© The Author(s). 2017