Early human embryonic development: Blastocyst formation to gastrulation

Rossant, Janet; Tam, Patrick

doi:10.1016/j.devcel.2021.12.022

Cited by 86 publications

(62 citation statements)

References 134 publications

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“…1a,d,e ; Extended Data Fig. 1a-c, Supplementary Video) , likely equivalent to the primary syncytium of the peri-implantation stage human embryo 22 . Human chorionic gonadotropin (hCG) is a critical pregnancy hormone and its α subunit, CGA , was specifically induced by STB ( Fig.…”

Section: Resultsmentioning

confidence: 97%

A Comprehensive Roadmap of Human Placental Development in vitro

Slamecka

Tristan

Ryu

et al. 2022

Preprint

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Human pluripotent stem cells (hPSCs) represent a powerful model system to study early developmental processes. However, lineage specification into trophectoderm (TE) remains poorly understood and access to well-characterized placental cells for biomedical research is limited, largely depending on fetal tissues or cancer cell lines. Here, we developed novel strategies enabling highly efficient TE specification that generates cytotrophoblast (CTB) and multinucleated primary syncytiotrophoblast (STB) followed by establishment of trophoblast stem cells (TSCs) capable of differentiating into extravillous trophoblast (EVT) and STB after long-term expansion. We confirmed stepwise induction of lineage- and cell-type-specific genes and substantiated typical features of placental cells using morphological, biochemical, integrated multi-omics, and single-cell analyses. Our data provide conclusive evidence that conventional hPSCs can be directly and exclusively converted into TE, thereby providing an unlimited source of diverse placental cell types suitable for a broad range of biomedical applications.

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Section: Resultsmentioning

confidence: 97%

A Comprehensive Roadmap of Human Placental Development in vitro

Slamecka

Tristan

Ryu

et al. 2022

Preprint

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“…Mutations in genes encoding key cardiac transcription factors (TF) cause compartment-specific congenital defects, where autonomous and non-autonomous effects are difficult to disentangle. Moreover, species- specific variations in TF expression and function are becoming increasingly clear in the embryonic development (Rossant and Tam, 2022). To genetically validate the specificity of the human cardioid compartment platform, we next generated knockout (KO) hPSC lines for the prominent TFs ISL1 (Figure S6A) or TBX5 (Figure S6G) and for FOXF1 (Figure S6J), which is less characterized.…”

Section: Resultsmentioning

confidence: 99%

“…Interactions between cardiac lineages during the earliest stages of heart development, including cardiac mesoderm specification, morphogenesis, and functional differentiation, are notoriously difficult to analyze and inaccessible in human embryos. In addition, studies of human embryo development reveal a growing list of differences between species in expression patterns of critical developmental and functionality genes (Cui et al, 2019; Rossant and Tam, 2022; Verheule and Kaese, 2013). Such aspects are key to understanding the human-specific impact of mutations and teratogens on early human heart development and how this causes embryo failure.…”

Section: Discussionmentioning

confidence: 99%

Multi-chamber cardioids unravel human heart development and cardiac defects

Schmidt

Deyett

Ilmer

et al. 2022

Preprint

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The number one cause of human fetal death are defects in heart development. Because the human embryonic heart is inaccessible, and the impacts of mutations, drugs, and environmental factors on the specialized functions of different heart compartments are not captured by in vitro models, determining the underlying causes is difficult. Here, we established a human cardioid platform that recapitulates the development of all major embryonic heart compartments, including right and left ventricles, atria, outflow tract, and atrioventricular canal. By leveraging both 2D and 3D differentiation, we efficiently generated progenitor subsets with distinct first, anterior, and posterior second heart field identities. This advance enabled the reproducible generation of cardioids with compartment-specific in vivo-like gene expression profiles, morphologies, and functions. We used this platform to unravel the ontogeny of signal and contraction propagation between interacting heart chambers and dissect how genetic and environmental factors cause region-specific defects in the developing human heart.

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“…On the other hand, the extraembryonic ectoderm promotes the induction and specific positioning of the AVE ( Richardson et al, 2006 ; Rodriguez et al, 2005 ). Thus, the amniotic epithelium could be the equivalent to the extraembryonic ectoderm in primates and has a direct or indirect function in regulating the anterior regionalization of the epiblast ( Rossant and Tam, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

The human amniotic epithelium confers a bias to differentiate toward the neuroectoderm lineage in human embryonic stem cells

Ávila-González

Portillo

Barragán-Álvarez

et al. 2022

eLife

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Human embryonic stem cells (hESC) derive from the epiblast and have pluripotent potential. To maintain the conventional conditions of the pluripotent potential in an undifferentiated state, inactivated mouse embryonic fibroblast (iMEF) is used as a feeder layer. However, it has been suggested that hESC under this conventional condition (hESC-iMEF) is an artifact that does not correspond to the in vitro counterpart of the human epiblast. Our previous studies demonstrated the use of an alternative feeder layer of human amniotic epithelial cells (hAEC) to derive and maintain hESC. We wondered if the hESC-hAEC culture could represent a different pluripotent stage than that of naïve or primed conventional conditions, simulating the stage in which the amniotic epithelium derives from the epiblast during peri-implantation. Like the conventional primed hESC-iMEF, hESC-hAEC has the same levels of expression as the 'pluripotency core'; and does not express markers of naïve pluripotency. However, it presents a downregulation of HOX genes and genes associated with the endoderm and mesoderm and it exhibits an increase in the expression of ectoderm lineage genes, specifically in the anterior neuroectoderm. Transcriptome analysis showed in hESC-hAEC an upregulated signature of genes coding for transcription factors involved in neural induction and forebrain development, and the ability to differentiate into a neural lineage was superior in comparison with conventional hESC-iMEF. We propose that the interaction of hESC with hAEC confers hESC a biased potential that resembles the anteriorized epiblast, which is predisposed to form the neural ectoderm.

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Early human embryonic development: Blastocyst formation to gastrulation

Cited by 86 publications

References 134 publications

A Comprehensive Roadmap of Human Placental Development in vitro

A Comprehensive Roadmap of Human Placental Development in vitro

Multi-chamber cardioids unravel human heart development and cardiac defects

The human amniotic epithelium confers a bias to differentiate toward the neuroectoderm lineage in human embryonic stem cells

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