Cell Reports, Journal Year: 2022, Volume and Issue: 39(12), P. 110994 - 110994
Published: June 1, 2022
Language: Английский
Cell, Journal Year: 2022, Volume and Issue: 185(18), P. 3290 - 3306.e25
Published: Aug. 2, 2022
In vitro cultured stem cells with distinct developmental capacities can contribute to embryonic or extraembryonic tissues after microinjection into pre-implantation mammalian embryos. However, whether independently give rise entire gastrulating embryo-like structures and compartments remains unknown. Here, we adapt a recently established platform for prolonged ex utero growth of natural embryos generate mouse post-gastrulation synthetic whole embryo models (sEmbryos), both compartments, starting solely from naive ESCs. This was achieved by co-aggregating non-transduced ESCs, ESCs transiently expressing Cdx2 Gata4 promote their priming toward trophectoderm primitive endoderm lineages, respectively. sEmbryos adequately accomplish gastrulation, advance through key milestones, develop organ progenitors within complex similar E8.5 stage Our findings highlight the plastic potential pluripotent self-organize functionally reconstitute model beyond gastrulation.
Language: Английский
Citations
166
Nature, Journal Year: 2023, Volume and Issue: 622(7983), P. 584 - 593
Published: June 27, 2023
Abstract The human embryo undergoes morphogenetic transformations following implantation into the uterus, but our knowledge of this crucial stage is limited by inability to observe in vivo. Models derived from stem cells are important tools for interrogating developmental events and tissue–tissue crosstalk during these stages 1 . Here we establish a model post-implantation embryo, embryoid, comprising embryonic extraembryonic tissues. We combine two types extraembryonic-like cell generated overexpression transcription factors with wild-type promote their self-organization structures that mimic several aspects embryo. These self-organized aggregates contain pluripotent epiblast-like domain surrounded Our functional studies demonstrate robustly differentiates amnion, mesenchyme primordial germ cell-like response bone protein cues. In addition, identify an inhibitory role SOX17 specification anterior hypoblast-like 2 Modulation subpopulations compartment demonstrates influence differentiation, highlighting crosstalk. conclusion, present modular, tractable, integrated 3 will enable us probe key questions development, critical window which substantial numbers pregnancies fail.
Language: Английский
Citations
136
Developmental Cell, Journal Year: 2022, Volume and Issue: 57(2), P. 152 - 165
Published: Jan. 1, 2022
Language: Английский
Citations
132
Nature, Journal Year: 2023, Volume and Issue: unknown
Published: Sept. 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.
Language: Английский
Citations
109
Nature, Journal Year: 2023, Volume and Issue: 622(7983), P. 574 - 583
Published: June 27, 2023
Abstract Investigating human development is a substantial scientific challenge due to the technical and ethical limitations of working with embryonic samples. In face these difficulties, stem cells have provided an alternative experimentally model inaccessible stages in vitro 1–13 . Here we show that pluripotent can be triggered self-organize into three-dimensional structures recapitulate some key spatiotemporal events early post-implantation development. Our system reproducibly captures spontaneous differentiation co-development epiblast-like extra-embryonic hypoblast-like lineages, establishes signalling hubs secreted modulators undergoes symmetry breaking-like events. Single-cell transcriptomics confirms diverse cell states perigastrulating embryo 14,15 without establishing placental types, including signatures epiblast, amniotic ectoderm, primitive streak, mesoderm, endoderm, as well initial yolk sac induction. Collectively, our features spanning from Carnegie stage 16 4–7, offering reproducible, tractable scalable experimental platform understand basic cellular molecular mechanisms underlie development, new opportunities dissect congenital pathologies high throughput.
Language: Английский
Citations
92
Cell stem cell, Journal Year: 2022, Volume and Issue: 29(5), P. 744 - 759.e6
Published: April 18, 2022
In primates, the amnion emerges through cavitation of epiblast during implantation, whereas in other species it does so later at gastrulation by folding ectoderm. How mechanisms amniogenesis diversified evolution remains unknown. Unexpectedly, single-cell analysis primate embryos uncovered two transcriptionally and temporally distinct waves. To study this, we employed naive-to-primed transition human pluripotent stem cells (hPSCs) to model peri-implantation development. Partially primed hPSCs transiently gained ability differentiate into cavitating epithelium that morphologically matched early amnion, fully produced resembling late instead, thus recapitulating independent differentiation The wave follows a trophectoderm-like pathway encompasses cavitation, resembles an ectoderm-like route gastrulation. discovery waves explains how could emerge via duplication pre-existing trophectoderm program.
Language: Английский
Citations
76
Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(6)
Published: June 1, 2022
Human pregnancy depends on the proper development of embryo prior to implantation and into uterine wall. During pre-implantation phase, formation morula is followed by internalization blastomeres that differentiate pluripotent inner cell mass lineage, while cells surface undergo polarization trophectoderm blastocyst. The mediates apposition adhesion blastocyst epithelium. These processes lead a stable contact between embryonic maternal tissues, resulting in new organ, placenta. implantation, start form basis for multiple specialized trophoblast subpopulations, all which fulfilling specific key functions placentation. They either polar serving typical epithelial functions, or apolar invasive adapt wall progressing pregnancy. composition these subpopulations crucial human placenta alterations are suggested result placenta-associated pathologies. This review article focuses what known about very early reproduction emphasizes morphological functional aspects differentiation subpopulations.
Language: Английский
Citations
76
Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)
Published: April 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
Language: Английский
Citations
75
Cell, Journal Year: 2023, Volume and Issue: 186(18), P. 3776 - 3792.e16
Published: July 20, 2023
Language: Английский
Citations
66
Cell stem cell, Journal Year: 2023, Volume and Issue: 30(5), P. 571 - 591
Published: May 1, 2023
Human pluripotent stem cells (hPSCs) and three-dimensional organoids have ushered in a new era for disease modeling drug discovery. Over the past decade, significant progress has been deriving functional from hPSCs, which applied to recapitulate phenotypes. In addition, these advancements extended application of hPSCs screening clinical-trial safety evaluations. This review provides an overview achievements challenges using hPSC-derived conduct relevant high-throughput, high-contentscreens evaluation. These studies greatly enhanced our knowledge toolbox precision medicine.
Language: Английский
Citations
64