Establishment of Trophoblast‐Like Tissue Model from Human Pluripotent Stem Cells in Three‐Dimensional Culture System

Abstract The placenta has a lifelong impact on the health of both the mother and fetus. Despite its significance, human early placental development is poorly understood due to the limited models. The models that can reflect the key features of early human placental development, especially at early g...

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Main Authors: Kangli Cui, Yujuan Zhu, Yang Shi, Tingwei Chen, Hui Wang, Yaqiong Guo, Pengwei Deng, Haitao Liu, Xiaoguang Shao, Jianhua Qin
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202100031
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author Kangli Cui
Yujuan Zhu
Yang Shi
Tingwei Chen
Hui Wang
Yaqiong Guo
Pengwei Deng
Haitao Liu
Xiaoguang Shao
Jianhua Qin
author_facet Kangli Cui
Yujuan Zhu
Yang Shi
Tingwei Chen
Hui Wang
Yaqiong Guo
Pengwei Deng
Haitao Liu
Xiaoguang Shao
Jianhua Qin
author_sort Kangli Cui
collection DOAJ
description Abstract The placenta has a lifelong impact on the health of both the mother and fetus. Despite its significance, human early placental development is poorly understood due to the limited models. The models that can reflect the key features of early human placental development, especially at early gestation, are still lacking. Here, the authors report the generation of trophoblast‐like tissue model from human pluripotent stem cells (hPSCs) in three‐dimensional (3D) cultures. hPSCs efficiently self‐organize into blastocoel‐like cavities under defined conditions, which produce different trophoblast subtypes, including cytotrophoblasts (CTBs), syncytiotrophoblasts (STBs), and invasive extravillous trophoblasts (EVTs). The 3D cultures can exhibit microvilli structure and secrete human placenta‐specific hormone. Single‐cell RNA sequencing analysis further identifies the presence of major cell types of trophoblast‐like tissue as existing in vivo. The results reveal the feasibility to establish 3D trophoblast‐like tissue model from hPSCs in vitro, which is not obtained by monolayer culture. This new model system can not only facilitate to dissect the underlying mechanisms of early human placental development, but also imply its potential for study in developmental biology and gestational disorders.
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spelling doaj.art-d650d277e3044c64b3124450ebc3579c2022-12-21T19:44:34ZengWileyAdvanced Science2198-38442022-01-0193n/an/a10.1002/advs.202100031Establishment of Trophoblast‐Like Tissue Model from Human Pluripotent Stem Cells in Three‐Dimensional Culture SystemKangli Cui0Yujuan Zhu1Yang Shi2Tingwei Chen3Hui Wang4Yaqiong Guo5Pengwei Deng6Haitao Liu7Xiaoguang Shao8Jianhua Qin9Division of Biotechnology Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian 116023 ChinaDivision of Biotechnology Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian 116023 ChinaDalian Municipal Women and Children's Medical Center Dalian 116037 ChinaYunnan Key Laboratory of Primate Biomedical Research Institute of Primate Translational Medicine Kunming University of Science and Technology Kunming 650031 ChinaDivision of Biotechnology Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian 116023 ChinaDivision of Biotechnology Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian 116023 ChinaDivision of Biotechnology Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian 116023 ChinaDivision of Biotechnology Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian 116023 ChinaDalian Municipal Women and Children's Medical Center Dalian 116037 ChinaDivision of Biotechnology Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian 116023 ChinaAbstract The placenta has a lifelong impact on the health of both the mother and fetus. Despite its significance, human early placental development is poorly understood due to the limited models. The models that can reflect the key features of early human placental development, especially at early gestation, are still lacking. Here, the authors report the generation of trophoblast‐like tissue model from human pluripotent stem cells (hPSCs) in three‐dimensional (3D) cultures. hPSCs efficiently self‐organize into blastocoel‐like cavities under defined conditions, which produce different trophoblast subtypes, including cytotrophoblasts (CTBs), syncytiotrophoblasts (STBs), and invasive extravillous trophoblasts (EVTs). The 3D cultures can exhibit microvilli structure and secrete human placenta‐specific hormone. Single‐cell RNA sequencing analysis further identifies the presence of major cell types of trophoblast‐like tissue as existing in vivo. The results reveal the feasibility to establish 3D trophoblast‐like tissue model from hPSCs in vitro, which is not obtained by monolayer culture. This new model system can not only facilitate to dissect the underlying mechanisms of early human placental development, but also imply its potential for study in developmental biology and gestational disorders.https://doi.org/10.1002/advs.202100031human pluripotent stem cellsmatricesplacenta developmentthree‐dimensional culturestrophoblast tissues
spellingShingle Kangli Cui
Yujuan Zhu
Yang Shi
Tingwei Chen
Hui Wang
Yaqiong Guo
Pengwei Deng
Haitao Liu
Xiaoguang Shao
Jianhua Qin
Establishment of Trophoblast‐Like Tissue Model from Human Pluripotent Stem Cells in Three‐Dimensional Culture System
Advanced Science
human pluripotent stem cells
matrices
placenta development
three‐dimensional cultures
trophoblast tissues
title Establishment of Trophoblast‐Like Tissue Model from Human Pluripotent Stem Cells in Three‐Dimensional Culture System
title_full Establishment of Trophoblast‐Like Tissue Model from Human Pluripotent Stem Cells in Three‐Dimensional Culture System
title_fullStr Establishment of Trophoblast‐Like Tissue Model from Human Pluripotent Stem Cells in Three‐Dimensional Culture System
title_full_unstemmed Establishment of Trophoblast‐Like Tissue Model from Human Pluripotent Stem Cells in Three‐Dimensional Culture System
title_short Establishment of Trophoblast‐Like Tissue Model from Human Pluripotent Stem Cells in Three‐Dimensional Culture System
title_sort establishment of trophoblast like tissue model from human pluripotent stem cells in three dimensional culture system
topic human pluripotent stem cells
matrices
placenta development
three‐dimensional cultures
trophoblast tissues
url https://doi.org/10.1002/advs.202100031
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