Pluripotent stem cell-derived endometrial stromal fibroblasts in a cyclic, hormone-responsive, coculture model of human decidua

Summary: Various human diseases and pregnancy-related disorders reflect endometrial dysfunction. However, rodent models do not share fundamental biological processes with the human endometrium, such as spontaneous decidualization, and no existing human cell cultures recapitulate the cyclic interacti...

Full description

Bibliographic Details
Main Authors: Virginia Chu Cheung, Chian-Yu Peng, Mirna Marinić, Noboru J. Sakabe, Ivy Aneas, Vincent J. Lynch, Carole Ober, Marcelo A. Nobrega, John A. Kessler
Format: Article
Language:English
Published: Elsevier 2021-05-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124721004770
_version_ 1818455358072422400
author Virginia Chu Cheung
Chian-Yu Peng
Mirna Marinić
Noboru J. Sakabe
Ivy Aneas
Vincent J. Lynch
Carole Ober
Marcelo A. Nobrega
John A. Kessler
author_facet Virginia Chu Cheung
Chian-Yu Peng
Mirna Marinić
Noboru J. Sakabe
Ivy Aneas
Vincent J. Lynch
Carole Ober
Marcelo A. Nobrega
John A. Kessler
author_sort Virginia Chu Cheung
collection DOAJ
description Summary: Various human diseases and pregnancy-related disorders reflect endometrial dysfunction. However, rodent models do not share fundamental biological processes with the human endometrium, such as spontaneous decidualization, and no existing human cell cultures recapitulate the cyclic interactions between endometrial stromal and epithelial compartments necessary for decidualization and implantation. Here we report a protocol differentiating human pluripotent stem cells into endometrial stromal fibroblasts (PSC-ESFs) that are highly pure and able to decidualize. Coculture of PSC-ESFs with placenta-derived endometrial epithelial cells generated organoids used to examine stromal-epithelial interactions. Cocultures exhibited specific endometrial markers in the appropriate compartments, organization with cell polarity, and hormone responsiveness of both cell types. Furthermore, cocultures recapitulate a central feature of the human decidua by cyclically responding to hormone withdrawal followed by hormone retreatment. This advance enables mechanistic studies of the cyclic responses that characterize the human endometrium.
first_indexed 2024-12-14T22:09:30Z
format Article
id doaj.art-f12da9fe6d524cb6bd0633fc2545a92b
institution Directory Open Access Journal
issn 2211-1247
language English
last_indexed 2024-12-14T22:09:30Z
publishDate 2021-05-01
publisher Elsevier
record_format Article
series Cell Reports
spelling doaj.art-f12da9fe6d524cb6bd0633fc2545a92b2022-12-21T22:45:48ZengElsevierCell Reports2211-12472021-05-01357109138Pluripotent stem cell-derived endometrial stromal fibroblasts in a cyclic, hormone-responsive, coculture model of human deciduaVirginia Chu Cheung0Chian-Yu Peng1Mirna Marinić2Noboru J. Sakabe3Ivy Aneas4Vincent J. Lynch5Carole Ober6Marcelo A. Nobrega7John A. Kessler8Department of Neurology, Northwestern University, Chicago, IL 60611, USA; Corresponding authorDepartment of Neurology, Northwestern University, Chicago, IL 60611, USADepartment of Human Genetics, University of Chicago, Chicago, IL, USA; Current address: Department of Organismal Biology and Anatomy, University of Chicago, Chicago, IL, USADepartment of Human Genetics, University of Chicago, Chicago, IL, USADepartment of Human Genetics, University of Chicago, Chicago, IL, USADepartment of Human Genetics, University of Chicago, Chicago, IL, USA; Department of Biological Sciences, University of Buffalo, Buffalo, NY, USADepartment of Human Genetics, University of Chicago, Chicago, IL, USADepartment of Human Genetics, University of Chicago, Chicago, IL, USADepartment of Neurology, Northwestern University, Chicago, IL 60611, USA; Corresponding authorSummary: Various human diseases and pregnancy-related disorders reflect endometrial dysfunction. However, rodent models do not share fundamental biological processes with the human endometrium, such as spontaneous decidualization, and no existing human cell cultures recapitulate the cyclic interactions between endometrial stromal and epithelial compartments necessary for decidualization and implantation. Here we report a protocol differentiating human pluripotent stem cells into endometrial stromal fibroblasts (PSC-ESFs) that are highly pure and able to decidualize. Coculture of PSC-ESFs with placenta-derived endometrial epithelial cells generated organoids used to examine stromal-epithelial interactions. Cocultures exhibited specific endometrial markers in the appropriate compartments, organization with cell polarity, and hormone responsiveness of both cell types. Furthermore, cocultures recapitulate a central feature of the human decidua by cyclically responding to hormone withdrawal followed by hormone retreatment. This advance enables mechanistic studies of the cyclic responses that characterize the human endometrium.http://www.sciencedirect.com/science/article/pii/S2211124721004770human pluripotent stem cellsendometrial stromal cellsdeciduaepithelial-stromal signalingcyclic hormone responsecell-cell signaling
spellingShingle Virginia Chu Cheung
Chian-Yu Peng
Mirna Marinić
Noboru J. Sakabe
Ivy Aneas
Vincent J. Lynch
Carole Ober
Marcelo A. Nobrega
John A. Kessler
Pluripotent stem cell-derived endometrial stromal fibroblasts in a cyclic, hormone-responsive, coculture model of human decidua
Cell Reports
human pluripotent stem cells
endometrial stromal cells
decidua
epithelial-stromal signaling
cyclic hormone response
cell-cell signaling
title Pluripotent stem cell-derived endometrial stromal fibroblasts in a cyclic, hormone-responsive, coculture model of human decidua
title_full Pluripotent stem cell-derived endometrial stromal fibroblasts in a cyclic, hormone-responsive, coculture model of human decidua
title_fullStr Pluripotent stem cell-derived endometrial stromal fibroblasts in a cyclic, hormone-responsive, coculture model of human decidua
title_full_unstemmed Pluripotent stem cell-derived endometrial stromal fibroblasts in a cyclic, hormone-responsive, coculture model of human decidua
title_short Pluripotent stem cell-derived endometrial stromal fibroblasts in a cyclic, hormone-responsive, coculture model of human decidua
title_sort pluripotent stem cell derived endometrial stromal fibroblasts in a cyclic hormone responsive coculture model of human decidua
topic human pluripotent stem cells
endometrial stromal cells
decidua
epithelial-stromal signaling
cyclic hormone response
cell-cell signaling
url http://www.sciencedirect.com/science/article/pii/S2211124721004770
work_keys_str_mv AT virginiachucheung pluripotentstemcellderivedendometrialstromalfibroblastsinacyclichormoneresponsivecoculturemodelofhumandecidua
AT chianyupeng pluripotentstemcellderivedendometrialstromalfibroblastsinacyclichormoneresponsivecoculturemodelofhumandecidua
AT mirnamarinic pluripotentstemcellderivedendometrialstromalfibroblastsinacyclichormoneresponsivecoculturemodelofhumandecidua
AT noborujsakabe pluripotentstemcellderivedendometrialstromalfibroblastsinacyclichormoneresponsivecoculturemodelofhumandecidua
AT ivyaneas pluripotentstemcellderivedendometrialstromalfibroblastsinacyclichormoneresponsivecoculturemodelofhumandecidua
AT vincentjlynch pluripotentstemcellderivedendometrialstromalfibroblastsinacyclichormoneresponsivecoculturemodelofhumandecidua
AT caroleober pluripotentstemcellderivedendometrialstromalfibroblastsinacyclichormoneresponsivecoculturemodelofhumandecidua
AT marceloanobrega pluripotentstemcellderivedendometrialstromalfibroblastsinacyclichormoneresponsivecoculturemodelofhumandecidua
AT johnakessler pluripotentstemcellderivedendometrialstromalfibroblastsinacyclichormoneresponsivecoculturemodelofhumandecidua