Complete human day 14 post-implantation embryo models from naive ES cells

Nature, Год журнала: 2023, Номер unknown

Опубликована: Сен. 6, 2023

The ability to study human post-implantation development remains limited owing ethical and technical challenges associated with intrauterine after implantation1. Embryo-like models spatially organized morphogenesis structure of all defining embryonic extra-embryonic tissues the conceptus (that is, disc, bilaminar yolk sac, chorionic sac surrounding trophoblast layer) remain lacking1,2. Mouse naive stem cells have recently been shown give rise capable self-assembling into post-gastrulation structured stem-cell-based embryo (called SEMs)3. Here we extend those findings humans using only genetically unmodified (cultured in enhanced cell medium conditions)4. Such fully integrated complete SEMs recapitulate organization nearly known lineages compartments embryos, including epiblast, hypoblast, mesoderm layer latter compartments. These demonstrated developmental growth dynamics that resemble key hallmarks stage embryogenesis up 13-14 days fertilization (Carnegie 6a). include disc formation, epiblast lumenogenesis, polarized amniogenesis, anterior-posterior symmetry breaking, primordial germ-cell specification, visceral parietal endoderm expansion defines a cavity connecting stalk, trophoblast-surrounding compartment demonstrating syncytium lacunae formation. This SEM platform will probably enable experimental investigation previously inaccessible windows early post implantation peri-gastrulation development.

Язык: Английский

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Modeling post-implantation stages of human development into early organogenesis with stem-cell-derived peri-gastruloids

Cell, Год журнала: 2023, Номер 186(18), С. 3776 - 3792.e16

Опубликована: Июль 20, 2023

Язык: Английский

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Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Апрель 26, 2024

The induced pluripotent stem cell (iPSC) technology has transformed in vitro research and holds great promise to advance regenerative medicine. iPSCs have the capacity for an almost unlimited expansion, are amenable genetic engineering, can be differentiated into most somatic types. been widely applied model human development diseases, perform drug screening, develop therapies. In this review, we outline key developments iPSC field highlight immense versatility of modeling therapeutic applications. We begin by discussing pivotal discoveries that revealed potential a nucleus reprogramming led successful generation iPSCs. consider molecular mechanisms dynamics as well numerous methods available induce pluripotency. Subsequently, discuss various iPSC-based cellular models, from mono-cultures single type complex three-dimensional organoids, how these models elucidate diseases. use examples neurological disorders, coronavirus disease 2019 (COVID-19), cancer diversity disease-specific phenotypes modeled using iPSC-derived cells. also used high-throughput screening toxicity studies. Finally, process developing autologous allogeneic therapies their alleviate

Язык: Английский

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3D-cultured blastoids model human embryogenesis from pre-implantation to early gastrulation stages

Cell stem cell, Год журнала: 2023, Номер 30(9), С. 1148 - 1165.e7

Опубликована: Сен. 1, 2023

Naive human pluripotent stem cells have the remarkable ability to self-organize into blastocyst-like structures ("blastoids") that model lineage segregation in pre-implantation embryo. However, extent which blastoids can recapitulate defining features of post-implantation development remains unexplored. Here, we report cultured on thick three-dimensional (3D) extracellular matrices capture hallmarks early development, including epiblast lumenogenesis, rapid expansion and diversification trophoblast lineages, robust invasion extravillous by day 14. Extended blastoid culture results localized activation primitive streak marker TBXT emergence embryonic germ layers 21. We also show modulation WNT signaling alters balance between fates blastoids. This work demonstrates 3D-cultured offer a continuous integrated vitro system extraembryonic from gastrulation stages.

Язык: Английский

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Epigenetic regulation of early human embryo development

Cell stem cell, Год журнала: 2023, Номер 30(12), С. 1569 - 1584

Опубликована: Окт. 18, 2023

Studies of mammalian development have advanced our understanding the genetic, epigenetic, and cellular processes that orchestrate embryogenesis uncovered new insights into unique aspects human embryogenesis. Recent studies now produced first epigenetic maps early embryogenesis, stimulating ideas about reprogramming, cell fate control, potential mechanisms underpinning developmental plasticity in embryos. In this review, we discuss these regulation importance for safeguarding development. We also highlight unanswered questions key challenges remain to be addressed.

Язык: Английский

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Hallmarks of totipotent and pluripotent stem cell states

Cell stem cell, Год журнала: 2024, Номер 31(3), С. 312 - 333

Опубликована: Фев. 20, 2024

Though totipotency and pluripotency are transient during early embryogenesis, they establish the foundation for development of all mammals. Studying these in vivo has been challenging due to limited access ethical constraints, particularly humans. Recent progress led diverse culture adaptations epiblast cells vitro form totipotent pluripotent stem cells, which not only deepen our understanding embryonic but also serve as invaluable resources animal reproduction regenerative medicine. This review delves into hallmarks shedding light on their key molecular functional features.

Язык: Английский

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3D reconstruction of a gastrulating human embryo

Cell, Год журнала: 2024, Номер 187(11), С. 2855 - 2874.e19

Опубликована: Апрель 23, 2024

Язык: Английский

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A Comprehensive Human Embryogenesis Reference Tool using Single-Cell RNA-Sequencing Data

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2021, Номер unknown

Опубликована: Май 7, 2021

Summary Stem cell-based embryo models offer unprecedented experimental tools for studying early human development. The usefulness of hinges on their molecular, cellular and structural fidelities to in vivo counterparts. To authenticate models, single-cell RNA-sequencing has been utilised unbiased transcriptional profiling. However, a well-organised integrated dataset, serving as universal reference benchmarking remains unavailable. Herein, we developed such reference, through integration six published datasets covering developmental stages from the zygote gastrula. Lineage annotations are contrasted validated with available non-human primate datasets. Using stabilised UMAP constructed web tool, where query can be projected annotated predicted cell identities. this examined several recent highlighting risk misannotation when relevant references lacking.

Язык: Английский

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Global Literature Analysis of Organoid and Organ‐on‐Chip Research

Advanced Healthcare Materials, Год журнала: 2023, Номер 13(21)

Опубликована: Июль 22, 2023

Organoids and cells in organ-on-chip platforms replicate higher-level anatomical, physiological, or pathological states of tissues organs. These technologies are widely regarded by academia, the pharmacological industry regulators as key biomedical developments. To map advances this emerging field, a literature analysis 16,000 article metadata based on quality-controlled text-mining algorithm is performed. The covers titles, keywords, abstracts categorized academic publications preprint databases published after 2010. identifies tracks 149 107 organs organ substructures modeled organoids organ-on-chip, respectively, stem cell sources, well 130 diseases, 16 groups organisms other than human mouse which organoid/organ-on-chip technology applied. illustrates changing diversity focus research captures its geographical distribution. downloadable dataset provided robust framework for researchers to interrogate with their own questions.

Язык: Английский

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Hypoblast from human pluripotent stem cells regulates epiblast development

Nature, Год журнала: 2023, Номер 626(7998), С. 357 - 366

Опубликована: Дек. 5, 2023

Abstract Recently, several studies using cultures of human embryos together with single-cell RNA-seq analyses have revealed differences between humans and mice, necessitating the study 1–8 . Despite importance embryology, ethical legal restrictions limited post-implantation-stage studies. Thus, recent efforts focused on developing in vitro self-organizing models stem cells 9–17 Here, we report genetic non-genetic approaches to generate authentic hypoblast (naive hPSC-derived hypoblast-like (nHyCs))—known give rise one two extraembryonic tissues essential for embryonic development—from naive pluripotent (hPSCs). Our nHyCs spontaneously assemble hPSCs form a three-dimensional bilaminar structure (bilaminoids) pro-amniotic-like cavity. In presence additional analogues second tissue, trophectoderm, efficiency bilaminoid formation increases from 20% 40%, epiblast within bilaminoids continues develop response trophectoderm-secreted IL-6. Furthermore, show that robustly recapitulate patterning anterior–posterior axis reflecting pregastrula stage, emergence which can be shaped by genetically manipulating DKK1/OTX2 domain. We therefore successfully modelled identified mechanisms efficiently guide stage-specific growth progression as it establishes post-implantation landmarks embryogenesis.

Язык: Английский

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