Generation of human blastocyst-like structures from pluripotent stem cells

Yong Fan; Zheying Min; Samhan M. Alsolami; Zhenglai Ma; E. Zhang; Wei Chen; Ke Zhong; Wendi Pei; Xiangjin Kang; Puyao Zhang; Yongliang Wang; Yingying Zhang; Linfeng Zhan; Haiying Zhu; Chenrui An; Rong Li; Jie Qiao; Tao Tan; Mo Li; Yang Yu

doi:10.1038/s41421-021-00316-8

Generation of human blastocyst-like structures from pluripotent stem cells

Yong Fan, Zheying Min, Samhan M. Alsolami, Zhenglai Ma, E. Zhang, Wei Chen, Ke Zhong, Wendi Pei, Xiangjin Kang, Puyao Zhang, Yongliang Wang, Yingying Zhang, Linfeng Zhan, Haiying Zhu, Chenrui An, Rong Li, Jie Qiao, Tao Tan, Mo Li, Yang Yu

Research output: Contribution to journal › Article › peer-review

80 Scopus citations

Abstract

Human blastocysts are comprised of the first three cell lineages of the embryo: trophectoderm, epiblast and primitive endoderm, all of which are essential for early development and organ formation. However, due to ethical concerns and restricted access to human blastocysts, a comprehensive understanding of early human embryogenesis is still lacking. To bridge this knowledge gap, a reliable model system that recapitulates early stages of human embryogenesis is needed. Here we developed a three-dimensional (3D), two-step induction protocol for generating blastocyst-like structures (EPS-blastoids) from human extended pluripotent stem (EPS) cells. Morphological and single-cell transcriptomic analyses revealed that EPS-blastoids contain key cell lineages and are transcriptionally similar to human blastocysts. Furthermore, EPS-blastoids are similar with human embryos that were cultured for 8 or 10 days in vitro, in terms of embryonic structures, cell lineages and transcriptomic profiles. In conclusion, we developed a scalable system to mimic human blastocyst development, which can potentially facilitate the study of early implantation failure that induced by developmental defects at early stage.

Original language	English (US)
Journal	Cell Discovery
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41421-021-00316-8
State	Published - Sep 7 2021

Bibliographical note

KAUST Repository Item: Exported on 2021-12-14
Acknowledged KAUST grant number(s): OSR
Acknowledgements: This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16020700), the National Key R&D Program of China (2019YFA0110804, 2017YFA0105001, 2016YFC1000601, 2018YFA0801400, 2018YFC1003203), the National Natural Science Fundation of China (81925013, 81971381, 81771580, 81571400, 82071723, 81871162), Guangdong Basic and Applied Basic Research Foundation (2021B1515020069) and Outstanding Overseas Returnees Fund of the Peking University Third Hospital (BYSYLXHG2019002). Work in the Li laboratory was supported by KAUST Office of Sponsored Research (OSR), under award number BAS/1/1080- 01. We thank the members of the Li lab, Jinna Xu, Baolei Yuan, Chongwei Bi, Xuan Zhou, Gerardo Ramos Mandujano, Khaled Alsayegh, Yingzi Zhang, Yeteng Tian, and KAUST Core Labs for their generous help in this research

Access to Document

10.1038/s41421-021-00316-8

https://repository.kaust.edu.sa/bitstream/10754/671117/1/Articlefile1.pdf

Cite this

@article{7eed7707f6e14939a57a4ddcbf6749c2,

title = "Generation of human blastocyst-like structures from pluripotent stem cells",

abstract = "Human blastocysts are comprised of the first three cell lineages of the embryo: trophectoderm, epiblast and primitive endoderm, all of which are essential for early development and organ formation. However, due to ethical concerns and restricted access to human blastocysts, a comprehensive understanding of early human embryogenesis is still lacking. To bridge this knowledge gap, a reliable model system that recapitulates early stages of human embryogenesis is needed. Here we developed a three-dimensional (3D), two-step induction protocol for generating blastocyst-like structures (EPS-blastoids) from human extended pluripotent stem (EPS) cells. Morphological and single-cell transcriptomic analyses revealed that EPS-blastoids contain key cell lineages and are transcriptionally similar to human blastocysts. Furthermore, EPS-blastoids are similar with human embryos that were cultured for 8 or 10 days in vitro, in terms of embryonic structures, cell lineages and transcriptomic profiles. In conclusion, we developed a scalable system to mimic human blastocyst development, which can potentially facilitate the study of early implantation failure that induced by developmental defects at early stage.",

author = "Yong Fan and Zheying Min and Alsolami, {Samhan M.} and Zhenglai Ma and E. Zhang and Wei Chen and Ke Zhong and Wendi Pei and Xiangjin Kang and Puyao Zhang and Yongliang Wang and Yingying Zhang and Linfeng Zhan and Haiying Zhu and Chenrui An and Rong Li and Jie Qiao and Tao Tan and Mo Li and Yang Yu",

note = "KAUST Repository Item: Exported on 2021-12-14 Acknowledged KAUST grant number(s): OSR Acknowledgements: This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16020700), the National Key R&D Program of China (2019YFA0110804, 2017YFA0105001, 2016YFC1000601, 2018YFA0801400, 2018YFC1003203), the National Natural Science Fundation of China (81925013, 81971381, 81771580, 81571400, 82071723, 81871162), Guangdong Basic and Applied Basic Research Foundation (2021B1515020069) and Outstanding Overseas Returnees Fund of the Peking University Third Hospital (BYSYLXHG2019002). Work in the Li laboratory was supported by KAUST Office of Sponsored Research (OSR), under award number BAS/1/1080- 01. We thank the members of the Li lab, Jinna Xu, Baolei Yuan, Chongwei Bi, Xuan Zhou, Gerardo Ramos Mandujano, Khaled Alsayegh, Yingzi Zhang, Yeteng Tian, and KAUST Core Labs for their generous help in this research",

year = "2021",

month = sep,

day = "7",

doi = "10.1038/s41421-021-00316-8",

language = "English (US)",

volume = "7",

journal = "Cell Discovery",

issn = "2056-5968",

publisher = "Springer Nature",

number = "1",

}

TY - JOUR

T1 - Generation of human blastocyst-like structures from pluripotent stem cells

AU - Fan, Yong

AU - Min, Zheying

AU - Alsolami, Samhan M.

AU - Ma, Zhenglai

AU - Zhang, E.

AU - Chen, Wei

AU - Zhong, Ke

AU - Pei, Wendi

AU - Kang, Xiangjin

AU - Zhang, Puyao

AU - Wang, Yongliang

AU - Zhang, Yingying

AU - Zhan, Linfeng

AU - Zhu, Haiying

AU - An, Chenrui

AU - Li, Rong

AU - Qiao, Jie

AU - Tan, Tao

AU - Li, Mo

AU - Yu, Yang

N1 - KAUST Repository Item: Exported on 2021-12-14 Acknowledged KAUST grant number(s): OSR Acknowledgements: This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16020700), the National Key R&D Program of China (2019YFA0110804, 2017YFA0105001, 2016YFC1000601, 2018YFA0801400, 2018YFC1003203), the National Natural Science Fundation of China (81925013, 81971381, 81771580, 81571400, 82071723, 81871162), Guangdong Basic and Applied Basic Research Foundation (2021B1515020069) and Outstanding Overseas Returnees Fund of the Peking University Third Hospital (BYSYLXHG2019002). Work in the Li laboratory was supported by KAUST Office of Sponsored Research (OSR), under award number BAS/1/1080- 01. We thank the members of the Li lab, Jinna Xu, Baolei Yuan, Chongwei Bi, Xuan Zhou, Gerardo Ramos Mandujano, Khaled Alsayegh, Yingzi Zhang, Yeteng Tian, and KAUST Core Labs for their generous help in this research

PY - 2021/9/7

Y1 - 2021/9/7

N2 - Human blastocysts are comprised of the first three cell lineages of the embryo: trophectoderm, epiblast and primitive endoderm, all of which are essential for early development and organ formation. However, due to ethical concerns and restricted access to human blastocysts, a comprehensive understanding of early human embryogenesis is still lacking. To bridge this knowledge gap, a reliable model system that recapitulates early stages of human embryogenesis is needed. Here we developed a three-dimensional (3D), two-step induction protocol for generating blastocyst-like structures (EPS-blastoids) from human extended pluripotent stem (EPS) cells. Morphological and single-cell transcriptomic analyses revealed that EPS-blastoids contain key cell lineages and are transcriptionally similar to human blastocysts. Furthermore, EPS-blastoids are similar with human embryos that were cultured for 8 or 10 days in vitro, in terms of embryonic structures, cell lineages and transcriptomic profiles. In conclusion, we developed a scalable system to mimic human blastocyst development, which can potentially facilitate the study of early implantation failure that induced by developmental defects at early stage.

AB - Human blastocysts are comprised of the first three cell lineages of the embryo: trophectoderm, epiblast and primitive endoderm, all of which are essential for early development and organ formation. However, due to ethical concerns and restricted access to human blastocysts, a comprehensive understanding of early human embryogenesis is still lacking. To bridge this knowledge gap, a reliable model system that recapitulates early stages of human embryogenesis is needed. Here we developed a three-dimensional (3D), two-step induction protocol for generating blastocyst-like structures (EPS-blastoids) from human extended pluripotent stem (EPS) cells. Morphological and single-cell transcriptomic analyses revealed that EPS-blastoids contain key cell lineages and are transcriptionally similar to human blastocysts. Furthermore, EPS-blastoids are similar with human embryos that were cultured for 8 or 10 days in vitro, in terms of embryonic structures, cell lineages and transcriptomic profiles. In conclusion, we developed a scalable system to mimic human blastocyst development, which can potentially facilitate the study of early implantation failure that induced by developmental defects at early stage.

UR - http://hdl.handle.net/10754/671117

UR - https://www.nature.com/articles/s41421-021-00316-8

UR - http://www.scopus.com/inward/record.url?scp=85114644025&partnerID=8YFLogxK

U2 - 10.1038/s41421-021-00316-8

DO - 10.1038/s41421-021-00316-8

M3 - Article

C2 - 34489415

SN - 2056-5968

VL - 7

JO - Cell Discovery

JF - Cell Discovery

IS - 1

ER -

Generation of human blastocyst-like structures from pluripotent stem cells

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this