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Embryo model completes gastrulation to neurulation and organogenesis
by
Hanna, Jacob H.
, Shendure, Jay
, Greenfeld, Hannah
, Hollfelder, Florian
, Tran, Martin
, De Jonghe, Joachim
, Martin, Beth K.
, Glover, David M.
, Amadei, Gianluca
, Aguilera-Castrejon, Alejandro
, Zernicka-Goetz, Magdalena
, Handford, Charlotte E.
, Qiu, Chengxiang
, Chen, Dong-Yuan
, Elowitz, Michael B.
in
13
/ 13/1
/ 13/100
/ 13/106
/ 13/109
/ 13/51
/ 14/1
/ 14/19
/ 14/32
/ 14/63
/ 631/136/2060
/ 631/136/2086/2126
/ 631/136/2086/2127
/ 631/532/1360
/ 631/532/2117
/ Allantois
/ Animals
/ Cardiomyocytes
/ Cell Lineage
/ Chorion
/ Cytology
/ Efficiency
/ Embryo, Mammalian - cytology
/ Embryo, Mammalian - embryology
/ Embryogenesis
/ Embryonic growth stage
/ Embryonic Stem Cells - cytology
/ Embryos
/ Endoderm - cytology
/ Endoderm - embryology
/ Gastrulation
/ Gene expression
/ Heart - embryology
/ Humanities and Social Sciences
/ Mesencephalon - embryology
/ Mice
/ Modelling
/ Models, Biological
/ Morphology
/ multidisciplinary
/ Neural tube
/ Neural Tube - embryology
/ Neurulation
/ Organogenesis
/ PAX6 Transcription Factor - deficiency
/ PAX6 Transcription Factor - genetics
/ Prosencephalon - embryology
/ Science
/ Science (multidisciplinary)
/ Somites - embryology
/ Stem cells
/ Tissue engineering
/ Yolk sac
2022
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Embryo model completes gastrulation to neurulation and organogenesis
by
Hanna, Jacob H.
, Shendure, Jay
, Greenfeld, Hannah
, Hollfelder, Florian
, Tran, Martin
, De Jonghe, Joachim
, Martin, Beth K.
, Glover, David M.
, Amadei, Gianluca
, Aguilera-Castrejon, Alejandro
, Zernicka-Goetz, Magdalena
, Handford, Charlotte E.
, Qiu, Chengxiang
, Chen, Dong-Yuan
, Elowitz, Michael B.
in
13
/ 13/1
/ 13/100
/ 13/106
/ 13/109
/ 13/51
/ 14/1
/ 14/19
/ 14/32
/ 14/63
/ 631/136/2060
/ 631/136/2086/2126
/ 631/136/2086/2127
/ 631/532/1360
/ 631/532/2117
/ Allantois
/ Animals
/ Cardiomyocytes
/ Cell Lineage
/ Chorion
/ Cytology
/ Efficiency
/ Embryo, Mammalian - cytology
/ Embryo, Mammalian - embryology
/ Embryogenesis
/ Embryonic growth stage
/ Embryonic Stem Cells - cytology
/ Embryos
/ Endoderm - cytology
/ Endoderm - embryology
/ Gastrulation
/ Gene expression
/ Heart - embryology
/ Humanities and Social Sciences
/ Mesencephalon - embryology
/ Mice
/ Modelling
/ Models, Biological
/ Morphology
/ multidisciplinary
/ Neural tube
/ Neural Tube - embryology
/ Neurulation
/ Organogenesis
/ PAX6 Transcription Factor - deficiency
/ PAX6 Transcription Factor - genetics
/ Prosencephalon - embryology
/ Science
/ Science (multidisciplinary)
/ Somites - embryology
/ Stem cells
/ Tissue engineering
/ Yolk sac
2022
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Embryo model completes gastrulation to neurulation and organogenesis
by
Hanna, Jacob H.
, Shendure, Jay
, Greenfeld, Hannah
, Hollfelder, Florian
, Tran, Martin
, De Jonghe, Joachim
, Martin, Beth K.
, Glover, David M.
, Amadei, Gianluca
, Aguilera-Castrejon, Alejandro
, Zernicka-Goetz, Magdalena
, Handford, Charlotte E.
, Qiu, Chengxiang
, Chen, Dong-Yuan
, Elowitz, Michael B.
in
13
/ 13/1
/ 13/100
/ 13/106
/ 13/109
/ 13/51
/ 14/1
/ 14/19
/ 14/32
/ 14/63
/ 631/136/2060
/ 631/136/2086/2126
/ 631/136/2086/2127
/ 631/532/1360
/ 631/532/2117
/ Allantois
/ Animals
/ Cardiomyocytes
/ Cell Lineage
/ Chorion
/ Cytology
/ Efficiency
/ Embryo, Mammalian - cytology
/ Embryo, Mammalian - embryology
/ Embryogenesis
/ Embryonic growth stage
/ Embryonic Stem Cells - cytology
/ Embryos
/ Endoderm - cytology
/ Endoderm - embryology
/ Gastrulation
/ Gene expression
/ Heart - embryology
/ Humanities and Social Sciences
/ Mesencephalon - embryology
/ Mice
/ Modelling
/ Models, Biological
/ Morphology
/ multidisciplinary
/ Neural tube
/ Neural Tube - embryology
/ Neurulation
/ Organogenesis
/ PAX6 Transcription Factor - deficiency
/ PAX6 Transcription Factor - genetics
/ Prosencephalon - embryology
/ Science
/ Science (multidisciplinary)
/ Somites - embryology
/ Stem cells
/ Tissue engineering
/ Yolk sac
2022
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Embryo model completes gastrulation to neurulation and organogenesis
Journal Article
Embryo model completes gastrulation to neurulation and organogenesis
2022
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Overview
Embryonic stem (ES) cells can undergo many aspects of mammalian embryogenesis in vitro
1
–
5
, but their developmental potential is substantially extended by interactions with extraembryonic stem cells, including trophoblast stem (TS) cells, extraembryonic endoderm stem (XEN) cells and inducible XEN (iXEN) cells
6
–
11
. Here we assembled stem cell-derived embryos in vitro from mouse ES cells, TS cells and iXEN cells and showed that they recapitulate the development of whole natural mouse embryo in utero up to day 8.5 post-fertilization. Our embryo model displays headfolds with defined forebrain and midbrain regions and develops a beating heart-like structure, a trunk comprising a neural tube and somites, a tail bud containing neuromesodermal progenitors, a gut tube, and primordial germ cells. This complete embryo model develops within an extraembryonic yolk sac that initiates blood island development. Notably, we demonstrate that the neurulating embryo model assembled from
Pax6
-knockout ES cells aggregated with wild-type TS cells and iXEN cells recapitulates the ventral domain expansion of the neural tube that occurs in natural, ubiquitous
Pax6
-knockout embryos. Thus, these complete embryoids are a powerful in vitro model for dissecting the roles of diverse cell lineages and genes in development. Our results demonstrate the self-organization ability of ES cells and two types of extraembryonic stem cells to reconstitute mammalian development through and beyond gastrulation to neurulation and early organogenesis.
Synthetic mouse embryos assembled from embryonic stem cells, trophoblast stem cells and induced extraembryonic endoderm stem cells closely recapitulate the development of wild-type and mutant natural mouse embryos up to embryonic day 8.5.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/1
/ 13/100
/ 13/106
/ 13/109
/ 13/51
/ 14/1
/ 14/19
/ 14/32
/ 14/63
/ Animals
/ Chorion
/ Cytology
/ Embryo, Mammalian - cytology
/ Embryo, Mammalian - embryology
/ Embryonic Stem Cells - cytology
/ Embryos
/ Humanities and Social Sciences
/ Mice
/ PAX6 Transcription Factor - deficiency
/ PAX6 Transcription Factor - genetics
/ Science
/ Yolk sac
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