TGF-β signaling in health and disease

Cell, Год журнала: 2023, Номер 186(19), С. 4007 - 4037

Опубликована: Сен. 1, 2023

The TGF-β regulatory system plays crucial roles in the preservation of organismal integrity. signaling controls metazoan embryo development, tissue homeostasis, and injury repair through coordinated effects on cell proliferation, phenotypic plasticity, migration, metabolic adaptation, immune surveillance multiple types shared ecosystems. Defects signaling, particularly epithelial cells, fibroblasts, disrupt tolerance, promote inflammation, underlie pathogenesis fibrosis cancer, contribute to resistance these diseases treatment. Here, we review how coordinates multicellular response programs health disease this knowledge can be leveraged develop treatments for system.

Язык: Английский

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Single-cell transcriptomic characterization of a gastrulating human embryo

Nature, Год журнала: 2021, Номер 600(7888), С. 285 - 289

Опубликована: Ноя. 17, 2021

Язык: Английский

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Transposable elements shape the evolution of mammalian development

Nature Reviews Genetics, Год журнала: 2021, Номер 22(11), С. 691 - 711

Опубликована: Авг. 5, 2021

Язык: Английский

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Spatiotemporal mapping of gene expression landscapes and developmental trajectories during zebrafish embryogenesis

Developmental Cell, Год журнала: 2022, Номер 57(10), С. 1284 - 1298.e5

Опубликована: Май 1, 2022

A major challenge in understanding vertebrate embryogenesis is the lack of topographical transcriptomic information that can help correlate microenvironmental cues within hierarchy cell-fate decisions. Here, we employed Stereo-seq to profile 91 zebrafish embryo sections covering six critical time points during first 24 h development, obtaining a total 152,977 spots at resolution 10 × 15 μm3 (close cellular size) with spatial coordinates. Meanwhile, identified modules and co-varying genes for specific tissue organizations. By performing integrated analysis scRNA-seq data from each point, reconstructed spatially resolved developmental trajectories transitions molecular changes embryogenesis. We further investigated distribution ligand-receptor pairs potentially important interactions development. Our study constitutes fundamental reference studies aiming understand

Язык: Английский

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Mouse embryo model derived exclusively from embryonic stem cells undergoes neurulation and heart development

Cell stem cell, Год журнала: 2022, Номер 29(10), С. 1445 - 1458.e8

Опубликована: Сен. 8, 2022

Several in vitro models have been developed to recapitulate mouse embryogenesis solely from embryonic stem cells (ESCs). Despite mimicking many aspects of early development, they fail capture the interactions between and extraembryonic tissues. To overcome this difficulty, we a ESC-based model that reconstitutes pluripotent ESC lineage two lineages post-implantation embryo by transcription-factor-mediated induction. This unified recapitulates developmental events day 5.5 8.5, including gastrulation; formation anterior-posterior axis, brain, beating heart structure; development tissues, yolk sac chorion. Comparing single-cell RNA sequencing individual structures with time-matched natural embryos identified remarkably similar transcriptional programs across but also showed when where diverges program. Our findings demonstrate an extraordinary plasticity ESCs self-organize generate whole-embryo-like structure.

Язык: Английский

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Cell fate decisions, transcription factors and signaling during early retinal development

Progress in Retinal and Eye Research, Год журнала: 2022, Номер 91, С. 101093 - 101093

Опубликована: Июль 8, 2022

The development of the vertebrate eyes is a complex process starting from anterior-posterior and dorso-ventral patterning anterior neural tube, resulting in formation eye field. Symmetrical separation field at plate followed by two symmetrical evaginations to generate pair optic vesicles. Next, reciprocal invagination vesicles with surface ectoderm-derived lens placodes generates double-layered cups. inner outer layers cups develop into retina retinal pigment epithelium (RPE), respectively. In vitro produced tissues, called organoids, are formed human pluripotent stem cells, mimicking major steps differentiation vivo. This review article summarizes recent progress our understanding early development, focusing on field, vesicles, Recent single-cell transcriptomic studies integrated classical vivo genetic functional uncover range cellular mechanisms underlying development. functions signal transduction pathways lineage-specific DNA-binding transcription factors dissected explain cell-specific regulatory cell fate determination during homeodomain (HD) Otx2, Pax6, Lhx2, Six3 Six6, which required for discussed detail. Comprehensive provides insight molecular basis developmental ocular anomalies, such as cup coloboma. Lastly, modeling inherited diseases using cell-derived organoids opportunities discover novel therapies diseases.

Язык: Английский

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Mammalian primordial germ cell specification

Development, Год журнала: 2021, Номер 148(6)

Опубликована: Март 15, 2021

The peri-implantation window of mammalian development is the crucial for primordial germ cell (PGC) specification. Whereas pre-implantation dynamics are relatively conserved between species, implantation marks a stage developmental divergence key model organisms, and thus potential variance in molecular mechanisms PGC In humans, specification very difficult to study vivo To address this, combined use human nonhuman primate embryos, stem cell-based embryo models essential determining origin PGCs, as comparative analyses equivalent stages mouse development. Understanding PGCs not only accurate modeling this process using cells, but also role global epigenetic reprogramming upon which sex-specific differentiation into gametes relies.

Язык: Английский

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Cellular dynamics of EMT: lessons from live in vivo imaging of embryonic development

Cell Communication and Signaling, Год журнала: 2021, Номер 19(1)

Опубликована: Июль 22, 2021

Abstract Epithelial-mesenchymal transition (EMT) refers to a process in which epithelial cells lose apical-basal polarity and loosen cell–cell junctions take on mesenchymal cell morphologies invasive properties that facilitate migration through extracellular matrix. EMT—and the reverse mesenchymal-epithelial (MET)—are evolutionarily conserved processes are used throughout embryonic development drive tissue morphogenesis. During adult life, EMT is activated close wounds after injury, but also can be by cancers promote metastasis. controlled several mechanisms depend context. In response signaling and/or interactions with local environment, undergoing make rapid changes kinase adaptor proteins, adhesion matrix molecules, gene expression. Many of these modulate localization, activity, or expression cytoskeletal proteins mediate shape motility. Since cellular during highly dynamic context-dependent, it ideal analyze this situ living organisms. Embryonic model organisms amenable live time-lapse microscopy, provides an opportunity watch as happens. Here, focus functions actin cytoskeleton, I review recent examples how vivo imaging has led new insights into EMT. At same time, highlight specific developmental embryos—gastrulation fly mouse embryos, neural crest zebrafish frog embryos—that provide platforms for visualizing dynamics addition, introduce Kupffer’s vesicle embryo system investigate MET. discuss systems have provided adherens junction remodeling, planar signaling, cadherin functions, organization EMT, not only important understanding development, cancer progression. These findings shed light feature strategies exploited future work identify

Язык: Английский

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Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming

Nature Physics, Год журнала: 2022, Номер 18(12), С. 1482 - 1493

Опубликована: Окт. 24, 2022

Abstract Embryo development requires biochemical signalling to generate patterns of cell fates and active mechanical forces drive tissue shape changes. However, how these processes are coordinated, patterning is preserved despite the cellular flows occurring during morphogenesis, remains poorly understood. Gastrulation a crucial embryonic stage that involves both internalization mesendoderm germ layer tissue. Here we show that, in zebrafish embryos, gradient Nodal orchestrates pattern-preserving movements by triggering motility-driven unjamming transition. In addition its role as morphogen determining embryo patterning, graded mechanically subdivides into small fraction highly protrusive leader cells, able autonomously internalize via local unjamming, less followers, which need be pulled inwards leaders. The further enforces code preferential adhesion coupling leaders their immediate resulting collective ordered mode preserves patterning. Integrating this dual minimal particle simulations quantitatively predicts physiological experimentally perturbed movements. This provides quantitative framework for morphogen-encoded transition can bidirectionally couple mechanics with complex three-dimensional morphogenesis.

Язык: Английский

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Decoding gene regulation in the mouse embryo using single-cell multi-omics

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Июнь 15, 2022

Abstract Following gastrulation, the three primary germ layers develop into major organs in a process known as organogenesis. Single-cell RNA sequencing has enabled profiling of gene expression dynamics these cell fate decisions, yet comprehensive map interplay between transcription factors and cis-regulatory elements is lacking, are underlying regulatory networks. Here we generate multi-omics atlas mouse early organogenesis by simultaneously chromatin accessibility from tens thousands single cells. We computational method to leverage multimodal readouts predict factor binding events elements, which then use infer networks that underpin lineage commitment events. Finally, show models can be used silico predictions effect perturbations. validate this experimentally showing Brachyury essential for differentiation neuromesodermal progenitors somitic mesoderm priming elements. The data set interactively explored at https://www.bioinformatics.babraham.ac.uk/shiny/shiny_multiome_organogenesis/

Язык: Английский

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