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Article ; Online: Publisher Correction: Pluripotent stem cell-derived model of the post-implantation human embryo.

Weatherbee, Bailey A T / Gantner, Carlos W / Iwamoto-Stohl, Lisa K / Daza, Riza M / Hamazaki, Nobuhiko / Shendure, Jay / Zernicka-Goetz, Magdalena

Nature

2023 Volume 621, Issue 7977, Page(s) E30

Language	English
Publishing date	2023-08-17
Publishing country	England
Document type	Published Erratum
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-023-06524-4
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Article ; Online: Modeling human embryo development with embryonic and extra-embryonic stem cells.

Weatherbee, Bailey A T / Cui, Tongtong / Zernicka-Goetz, Magdalena

Developmental biology

2020 Volume 474, Page(s) 91–99

Abstract: Early human post-implantation development involves extensive growth combined with a series of complex morphogenetic events. The lack of precise spatial and temporal control over these processes leads to pregnancy loss. Given the ethical and technical ... ...

Abstract	Early human post-implantation development involves extensive growth combined with a series of complex morphogenetic events. The lack of precise spatial and temporal control over these processes leads to pregnancy loss. Given the ethical and technical limitations in studying the natural human embryo, alternative approaches are needed to investigate mechanisms underlying this critical stage of human development. Here, we present an overview of the different stem cells and stem cell-derived models which serve as useful, albeit imperfect, tools in understanding human embryogenesis. Current models include stem cells that represent each of the three earliest lineages: human embryonic stem cells corresponding to the epiblast, hypoblast-like stem cells and trophoblast stem cells. We also review the use of human embryonic stem cells to model complex aspects of epiblast morphogenesis and differentiation. Additionally, we propose that the combination of both embryonic and extra-embryonic stem cells to form three-dimensional embryo models will provide valuable insights into cell-cell chemical and mechanical interactions that are essential for natural embryogenesis.
MeSH term(s)	Animals ; Embryo, Mammalian/cytology ; Embryo, Mammalian/metabolism ; Embryoid Bodies/cytology ; Embryoid Bodies/metabolism ; Embryonic Development ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Germ Layers/cytology ; Humans ; Stem Cells/cytology ; Stem Cells/metabolism ; Trophoblasts/cytology
Language	English
Publishing date	2020-12-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1114-9
ISSN	1095-564X ; 0012-1606
ISSN (online)	1095-564X
ISSN	0012-1606
DOI	10.1016/j.ydbio.2020.12.010
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Article ; Online: Pluripotent stem cell-derived model of the post-implantation human embryo.

Weatherbee, Bailey A T / Gantner, Carlos W / Iwamoto-Stohl, Lisa K / Daza, Riza M / Hamazaki, Nobuhiko / Shendure, Jay / Zernicka-Goetz, Magdalena

Nature

2023 Volume 622, Issue 7983, Page(s) 584–593

Abstract: The human embryo undergoes morphogenetic transformations following implantation into the uterus, but our knowledge of this crucial stage is limited by the inability to observe the embryo in vivo. Models of the embryo derived from stem cells are important ...

Abstract	The human embryo undergoes morphogenetic transformations following implantation into the uterus, but our knowledge of this crucial stage is limited by the inability to observe the embryo in vivo. Models of the embryo derived from stem cells are important tools for interrogating developmental events and tissue-tissue crosstalk during these stages
MeSH term(s)	Female ; Humans ; Pregnancy ; Bone Morphogenetic Proteins ; Cell Differentiation ; Embryo Implantation ; Embryo, Mammalian/cytology ; Embryo, Mammalian/embryology ; Embryoid Bodies/cytology ; Embryonic Development ; Germ Layers/cytology ; Germ Layers/embryology ; Human Embryonic Stem Cells/cytology ; Models, Biological ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Pluripotent Stem Cells/cytology
Chemical Substances	Bone Morphogenetic Proteins ; SOX17 protein, human ; Transcription Factors
Language	English
Publishing date	2023-06-27
Publishing country	England
Document type	Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-023-06368-y
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Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Expression of SARS-CoV-2 receptor

Weatherbee, Bailey A T / Glover, David M / Zernicka-Goetz, Magdalena

Open biology

2020 Volume 10, Issue 8, Page(s) 200162

Abstract: While initially recognized as causing respiratory disease, the SARS-CoV-2 virus also affects many other organs leading to other complications. It has emerged that advanced age and obesity are risk factors for complications but questions concerning the ... ...

Abstract	While initially recognized as causing respiratory disease, the SARS-CoV-2 virus also affects many other organs leading to other complications. It has emerged that advanced age and obesity are risk factors for complications but questions concerning the potential effects on fetal health and successful pregnancy for those infected with SARS-CoV-2 remain largely unanswered. Here, we examine human pre-gastrulation embryos to determine the expression patterns of the genes
MeSH term(s)	Angiotensin-Converting Enzyme 2 ; Betacoronavirus/isolation & purification ; Betacoronavirus/metabolism ; COVID-19 ; Coronavirus Infections/pathology ; Coronavirus Infections/transmission ; Coronavirus Infections/virology ; Embryo, Mammalian/metabolism ; Female ; Humans ; Pandemics ; Peptidyl-Dipeptidase A/genetics ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/pathology ; Pneumonia, Viral/transmission ; Pneumonia, Viral/virology ; Pregnancy ; Pregnancy Trimester, First ; SARS-CoV-2 ; Serine Endopeptidases/genetics ; Serine Endopeptidases/metabolism ; Single-Cell Analysis ; Trophoblasts/metabolism
Chemical Substances	Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-)
Keywords	covid19
Language	English
Publishing date	2020-08-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2630944-0
ISSN	2046-2441 ; 2046-2441
ISSN (online)	2046-2441
ISSN	2046-2441
DOI	10.1098/rsob.200162
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Book ; Online: Author response for "Expression of SARS-CoV-2 receptor ACE2 and the protease TMPRSS2 suggests susceptibility of the human embryo in the first trimester"

Bailey A. T. Weatherbee / David M. Glover / Magdalena Zernicka-Goetz

2020

Keywords	covid19
Publisher	The Royal Society
Publishing country	uk
Document type	Book ; Online
DOI	10.1098/rsob.200162/v2/response1
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Reconstructing aspects of human embryogenesis with pluripotent stem cells.

Sozen, Berna / Jorgensen, Victoria / Weatherbee, Bailey A T / Chen, Sisi / Zhu, Meng / Zernicka-Goetz, Magdalena

Nature communications

2021 Volume 12, Issue 1, Page(s) 5550

Abstract: Understanding human development is of fundamental biological and clinical importance. Despite its significance, mechanisms behind human embryogenesis remain largely unknown. Here, we attempt to model human early embryo development with expanded ... ...

Abstract	Understanding human development is of fundamental biological and clinical importance. Despite its significance, mechanisms behind human embryogenesis remain largely unknown. Here, we attempt to model human early embryo development with expanded pluripotent stem cells (EPSCs) in 3-dimensions. We define a protocol that allows us to generate self-organizing cystic structures from human EPSCs that display some hallmarks of human early embryogenesis. These structures mimic polarization and cavitation characteristic of pre-implantation development leading to blastocyst morphology formation and the transition to post-implantation-like organization upon extended culture. Single-cell RNA sequencing of these structures reveals subsets of cells bearing some resemblance to epiblast, hypoblast and trophectoderm lineages. Nevertheless, significant divergences from natural blastocysts persist in some key markers, and signalling pathways point towards ways in which morphology and transcriptional-level cell identities may diverge in stem cell models of the embryo. Thus, this stem cell platform provides insights into the design of stem cell models of embryogenesis.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Biomarkers/metabolism ; Blastocyst/cytology ; Blastocyst/metabolism ; Cell Culture Techniques ; Cell Lineage/genetics ; Embryo, Mammalian/anatomy & histology ; Embryo, Mammalian/cytology ; Embryo, Mammalian/metabolism ; Embryonic Development/genetics ; GATA3 Transcription Factor/genetics ; GATA3 Transcription Factor/metabolism ; Gene Expression ; Humans ; Models, Biological ; Phospholipase C beta/genetics ; Phospholipase C beta/metabolism ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/metabolism ; SOXB1 Transcription Factors/genetics ; SOXB1 Transcription Factors/metabolism ; SOXF Transcription Factors/genetics ; SOXF Transcription Factors/metabolism ; Sequence Analysis, RNA ; Single-Cell Analysis
Chemical Substances	Adaptor Proteins, Signal Transducing ; Biomarkers ; GATA3 Transcription Factor ; GATA3 protein, human ; PARD6A protein, human ; SOX17 protein, human ; SOX2 protein, human ; SOXB1 Transcription Factors ; SOXF Transcription Factors ; PLCB1 protein, human (EC 3.1.4.11) ; Phospholipase C beta (EC 3.1.4.11)
Language	English
Publishing date	2021-09-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-25853-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: High-Throughput Transcriptomics of

Siddam, Archana D / Duot, Matthieu / Coomson, Sarah Y / Anand, Deepti / Aryal, Sandeep / Weatherbee, Bailey A T / Audic, Yann / Paillard, Luc / Lachke, Salil A

Cells

2023 Volume 12, Issue 7

Abstract: Defects in the development of the ocular lens can cause congenital cataracts. To understand the various etiologies of congenital cataracts, it is important to characterize the genes linked to this developmental defect and to define their downstream ... ...

Abstract	Defects in the development of the ocular lens can cause congenital cataracts. To understand the various etiologies of congenital cataracts, it is important to characterize the genes linked to this developmental defect and to define their downstream pathways that are relevant to lens biology and pathology. Deficiency or alteration of several RNA-binding proteins, including the conserved RBP Celf1 (CUGBP Elav-like family member 1), has been described to cause lens defects and early onset cataracts in animal models and/or humans. Celf1 is involved in various aspects of post-transcriptional gene expression control, including regulation of mRNA stability/decay, alternative splicing and translation.
MeSH term(s)	Animals ; Humans ; Mice ; Cataract/metabolism ; CELF1 Protein/genetics ; CELF1 Protein/metabolism ; Lens, Crystalline/metabolism ; Mice, Knockout ; RNA/metabolism ; Transcriptome/genetics
Chemical Substances	CELF1 Protein ; RNA (63231-63-0) ; CELF1 protein, mouse
Language	English
Publishing date	2023-04-01
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12071070
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Article ; Online: Expression of SARS-CoV-2 receptor ACE2 and the protease TMPRSS2 suggests susceptibility of the human embryo in the first trimester

Bailey A. T. Weatherbee / David M. Glover / Magdalena Zernicka-Goetz

Open Biology, Vol 10, Iss

2020 Volume 8

Abstract	While initially recognized as causing respiratory disease, the SARS-CoV-2 virus also affects many other organs leading to other complications. It has emerged that advanced age and obesity are risk factors for complications but questions concerning the potential effects on fetal health and successful pregnancy for those infected with SARS-CoV-2 remain largely unanswered. Here, we examine human pre-gastrulation embryos to determine the expression patterns of the genes ACE2, encoding the SARS-CoV-2 receptor, and TMPRSS2, encoding a protease that cleaves both the viral spike protein and the ACE2 receptor to facilitate infection. We show expression and co-expression of these genes in the trophoblast of the blastocyst and syncytiotrophoblast and hypoblast of the implantation stages, which develop into tissues that interact with the maternal blood supply for nutrient exchange. Expression of ACE2 and TMPRSS2 in these tissues raises the possibility for vertical transmission and indicates that further work is required to understand potential risks to implantation, placental health and fetal health that require further study.
Keywords	tmprss2 ; sars-cov-2 ; receptor ace2 ; Biology (General) ; QH301-705.5 ; covid19
Subject code	616
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	The Royal Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Distinct pathways drive anterior hypoblast specification in the implanting human embryo.

Weatherbee, Bailey A T / Weberling, Antonia / Gantner, Carlos W / Iwamoto-Stohl, Lisa K / Barnikel, Zoe / Barrie, Amy / Campbell, Alison / Cunningham, Paula / Drezet, Cath / Efstathiou, Panagiota / Fishel, Simon / Vindel, Sandra Gutiérrez / Lockwood, Megan / Oakley, Rebecca / Pretty, Catherine / Chowdhury, Nabiha / Richardson, Lucy / Mania, Anastasia / Weavers, Lauren /

Christie, Leila / Elder, Kay / Snell, Phillip / Zernicka-Goetz, Magdalena

Nature cell biology

2024 Volume 26, Issue 3, Page(s) 353–365

Abstract: Development requires coordinated interactions between the epiblast, which generates the embryo proper; the trophectoderm, which generates the placenta; and the hypoblast, which forms both the anterior signalling centre and the yolk sac. These ... ...

Abstract	Development requires coordinated interactions between the epiblast, which generates the embryo proper; the trophectoderm, which generates the placenta; and the hypoblast, which forms both the anterior signalling centre and the yolk sac. These interactions remain poorly understood in human embryogenesis because mechanistic studies have only recently become possible. Here we examine signalling interactions post-implantation using human embryos and stem cell models of the epiblast and hypoblast. We find anterior hypoblast specification is NODAL dependent, as in the mouse. However, while BMP inhibits anterior signalling centre specification in the mouse, it is essential for its maintenance in human. We also find contrasting requirements for BMP in the naive pre-implantation epiblast of mouse and human embryos. Finally, we show that NOTCH signalling is important for human epiblast survival. Our findings of conserved and species-specific factors that drive these early stages of embryonic development highlight the strengths of comparative species studies.
MeSH term(s)	Pregnancy ; Female ; Humans ; Germ Layers ; Embryo, Mammalian/metabolism ; Embryonic Development/genetics ; Signal Transduction ; Embryo Implantation
Language	English
Publishing date	2024-03-05
Publishing country	England
Document type	Journal Article
ZDB-ID	1474722-4
ISSN	1476-4679 ; 1465-7392
ISSN (online)	1476-4679
ISSN	1465-7392
DOI	10.1038/s41556-024-01367-1
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Article ; Online: High-Throughput Transcriptomics of Celf1 Conditional Knockout Lens Identifies Downstream Networks Linked to Cataract Pathology

Archana D. Siddam / Matthieu Duot / Sarah Y. Coomson / Deepti Anand / Sandeep Aryal / Bailey A. T. Weatherbee / Yann Audic / Luc Paillard / Salil A. Lachke

Cells, Vol 12, Iss 1070, p

2023 Volume 1070

Abstract	Defects in the development of the ocular lens can cause congenital cataracts. To understand the various etiologies of congenital cataracts, it is important to characterize the genes linked to this developmental defect and to define their downstream pathways that are relevant to lens biology and pathology. Deficiency or alteration of several RNA-binding proteins, including the conserved RBP Celf1 (CUGBP Elav-like family member 1), has been described to cause lens defects and early onset cataracts in animal models and/or humans. Celf1 is involved in various aspects of post-transcriptional gene expression control, including regulation of mRNA stability/decay, alternative splicing and translation. Celf1 germline knockout mice and lens conditional knockout ( Celf1 cKO ) mice develop fully penetrant cataracts in early postnatal stages. To define the genome-level changes in RNA transcripts that result from Celf1 deficiency, we performed high-throughput RNA-sequencing of Celf1 cKO mouse lenses at postnatal day (P) 0. Celf1 cKO lenses exhibit 987 differentially expressed genes (DEGs) at cut-offs of >1.0 log2 counts per million (CPM), ≥±0.58 log2 fold-change and <0.05 false discovery rate (FDR). Of these, 327 RNAs were reduced while 660 were elevated in Celf1 cKO lenses. The DEGs were subjected to various downstream analyses including iSyTE lens enriched-expression, presence in Cat-map, and gene ontology (GO) and representation of regulatory pathways. Further, a comparative analysis was done with previously generated microarray datasets on Celf1 cKO lenses P0 and P6. Together, these analyses validated and prioritized several key genes mis-expressed in Celf1 cKO lenses that are relevant to lens biology, including known cataract-linked genes (e.g., Cryab , Cryba2 , Cryba4 , Crybb1 , Crybb2 , Cryga , Crygb , Crygc , Crygd , Cryge , Crygf , Dnase2b , Bfsp1 , Gja3 , Pxdn , Sparc , Tdrd7 , etc.) as well as novel candidates (e.g., Ell2 and Prdm16 ). Together, these data have defined the alterations in lens transcriptome ...
Keywords	lens ; eye ; cataracts ; RNA-binding protein ; Cugbp1 ; development ; Biology (General) ; QH301-705.5
Subject code	333
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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