3D reconstruction of a gastrulating human embryo

Cell, Journal Year: 2024, Volume and Issue: 187(11), P. 2855 - 2874.e19

Published: April 23, 2024

Language: Английский

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A transcriptomic hourglass in brown algae

Nature, Journal Year: 2024, Volume and Issue: 635(8037), P. 129 - 135

Published: Oct. 23, 2024

Complex multicellularity has emerged independently across a few eukaryotic lineages and is often associated with the rise of elaborate, tightly coordinated developmental processes

Language: Английский

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Degrees of freedom: temperature’s influence on developmental rate

Current Opinion in Genetics & Development, Journal Year: 2024, Volume and Issue: 85, P. 102155 - 102155

Published: Feb. 9, 2024

Temperature exerts a fundamental influence across scales of biology, from the biophysical nature molecules, to sensitivity cells, and coordinated progression development in embryos. Species-specific developmental rates temperature-induced acceleration indicate that these sensing mechanisms are harnessed dynamics. Tracing how temperature propagates through biological pace can therefore reveal embryogenesis remains robust environmental influences. Cellular protein homeostasis (proteostasis), cellular metabolic rate linked both species-specific tempos specific cell types, hinting toward generalized timing control. New methods extract information single-cell profiling experiments driving further progress understanding direct cell-autonomous responses, coordination evolutionary modifications timing.

Language: Английский

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Temporal BMP4 effects on mouse embryonic and extraembryonic development

Nature, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

The developing placenta, which in mice originates through the extraembryonic ectoderm (ExE), is essential for mammalian embryonic development. Yet unbiased characterization of differentiation dynamics ExE and its interactions with embryo proper remains incomplete. Here we develop a temporal single-cell model mouse gastrulation that maps continuous parallel lineages. This matched three-way perturbation approach to target signalling from proper, alone, or both. We show specification involves early spatial transcriptional bifurcation uncommitted ectoplacental cone cells chorion progenitors. Early BMP4 progenitors required later their towards trophoblast giant cells. also find biphasic regulation by embryo. ExE-originating signal necessary mesoendoderm allantois primordial germ cell specification. However, commencing at day 7.5, embryo-derived restricts pool size favouring mesoderm precursors an fate. tissues are therefore entangled time, space axes, highlighting importance integrated understanding modelling vivo vitro.

Language: Английский

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A single-cell atlas of pig gastrulation as a resource for comparative embryology

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 18, 2024

Abstract Cell-fate decisions during mammalian gastrulation are poorly understood outside of rodent embryos. The embryonic disc pig embryos mirrors humans, making them a useful proxy for studying gastrulation. Here we present single-cell transcriptomic atlas gastrulation, revealing cell-fate emergence dynamics, as well conserved and divergent gene programs governing early porcine, primate, murine development. We highlight heterochronicity in extraembryonic cell-types, despite the broad conservation cell-type-specific transcriptional programs. apply these findings combination with functional investigations, to outline spatial, molecular, temporal events definitive endoderm specification. find FOXA2 + /TBXT- cells directly form endoderm, contrasting later-emerging FOXA2/TBXT+ node/notochord progenitors. Unlike mesoderm, none progenitors undergo epithelial-to-mesenchymal transition. Endoderm/Node fate hinges on balanced WNT hypoblast-derived NODAL, which is extinguished upon endodermal differentiation. These emphasise interplay between topological signalling determination

Language: Английский

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Inverse hourglass pattern of conservation in rodent molar development.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

ABSTRACT Although it is well established that certain stages of development are more conserved than others, the reasons for this phenomenon remain largely unknown. We study molecular conservation in an organ, molar, by comparing temporal profiles expression mice and hamsters. find molar characterized a rarely observed pattern level coding sequences forming inverse hourglass, with at beginning end morphogenesis intermediate stages. As rodent described, we were able to link properties expressed genes activity different developmental processes. Early late mobilize sets pleiotropic genes, cell division bud growth secretion tooth mineralization. The particularities dental homeostasis, degradation tissues hosting immune cells, as heterochronies linked adaptations, also probably contribute pattern. Our actors explains inverted hourglass molars combination processes intrinsic teeth, negative positive selection which mostly extrinsic teeth. This likely translatable explain patterns many other biological systems.

Language: Английский

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Scaling Autologous Epidermal Cell Therapies: iPSC‐Derived Keratinocytes and In Vivo Chimerism for Skin Regeneration

Experimental Dermatology, Journal Year: 2025, Volume and Issue: 34(5)

Published: April 27, 2025

ABSTRACT Severe skin injuries and genetic disorders such as epidermolysis bullosa present significant clinical challenges due to limitations in current epidermal replacement therapies. While promising, cultured epithelial autografts (CEAs) suffer from prolonged culture times, cellular senescence, low‐quality outcomes, limiting their widespread application. Recent advancements iPSC‐derived keratinocytes (iKeratinocytes) vivo chimerism offer transformative potential for scalable personalised regeneration. Advances understanding transcriptional networks, mRNA delivery, CRISPR‐based genome editing, automated biomanufacturing processes can enable improved efficient protocols generating iKeratinocytes. Despite these advances, there are still scaling iKeratinocytes, including optimising xeno‐free systems developing reproducible methods multilayered with appendages. Interspecies utilising lineage‐specific ablation targeted utero delivery of organ progenitor cells human tissue development within animal hosts, offering an alternative novel platform cell generation. This method, however, requires further refinements complete detachment target the hosts integration chimeric models. Together, iKeratinocytes hold great promise advancing autologous therapies enabling broader adoption outcomes patients severe disorders.

Language: Английский

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A single-cell chromatin accessibility dataset of human primed and naïve pluripotent stem cell-derived teratoma

Scientific Data, Journal Year: 2024, Volume and Issue: 11(1)

Published: July 2, 2024

Teratoma, due to its remarkable ability differentiate into multiple cell lineages, is a valuable model for studying human embryonic development. The similarity of the gene expression and chromatin accessibility patterns in these cells those observed vivo further underscores potential as research tool. Notably, teratomas derived from naïve (pre-implantation epiblast-like) pluripotent stem (PSCs) have larger diversity contain extraembryonic making them more suitable study developmental processes. However, type-specific epigenetic profiles PSC not been yet characterized. Using single-cell assay transposase-accessible sequencing (scATAC-seq), we analyzed 66,384 five PSCs their post-implantation epiblast-like (primed) counterparts. We 17 distinct types both resembling corresponding fetal tissues. Additionally, identified key transcription factors specific different types. Our dataset provides resource investigating regulatory programs relevant

Language: Английский

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A Transcriptomic Hourglass In Brown Algae

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 22, 2024

Abstract Complex multicellularity has emerged independently across a few eukaryotic lineages and is often associated with the rise of elaborate, tightly coordinated developmental processes. How development are interconnected in evolution major question biology. The hourglass model embryonic depicts how processes conserved during evolution, predicting morphological molecular divergence early late embryo stages, bridged by mid-embryonic (phylotypic) period linked to formation basic body plan. Initially found animal embryos, patterns have recently been proposed for land plants fungi. However, whether pattern an intrinsic feature all developmentally complex remains elusive. Here, we tested prevalence (molecular) brown algae, third most lineage on earth that evolved from animals, fungi, plants. By exploring evolutionary transcriptome algae distinct complexities, uncovered embryogenesis species. Filamentous without canonical display multicellular stages life cycle, whereas unicellular more rapidly evolving. Our findings suggest conservation cell differentiation but not necessarily embryogenesis. Together previous work provide further evidence generality eukaryotes.

Language: Английский

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Interspecies control of development during mammalian gastrulation

Emerging Topics in Life Sciences, Journal Year: 2023, Volume and Issue: 7(4), P. 397 - 408

Published: Nov. 7, 2023

Gastrulation represents a pivotal phase of development and aberrations during this period can have major consequences, from minor anatomical deviations to severe congenital defects. Animal models are used study gastrulation, however, there is considerable morphological molecular diversity gastrula across mammalian species. Here, we provide an overview the latest research on interspecies developmental control mammals. This includes single-cell atlases several which enabled comparisons temporal dynamics differentiation. These studies highlight conserved cell differentiation regulators both absolute relative differences in between Recent advances vitro culture techniques facilitated derivation, maintenance lines range species creation multi-species gastrulation. Gastruloids three-dimensional aggregates capable self-organising recapitulating aspects Such enable outside confines embryo. We recent evidence that processes such as somitogenesis neuronal maturation scale with known vivo tempo scaling likely due intrinsic biochemistry. also examples being influenced by extrinsic factors, including conditions, chimeric co-culture, xenotransplantation. collective underscore complexity gastrulation species, highlighting necessity additional datasets decipher intricate balance cellular programs signals shaping embryogenesis.

Language: Английский

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