EOMES establishes mesoderm and endoderm differentiation potential through SWI/SNF-mediated global enhancer remodeling DOI Creative Commons
Chiara M. Schröder, Lea Zissel, Sophie‐Luise Mersiowsky

и другие.

Developmental Cell, Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Mammalian pluripotent cells first segregate into neuroectoderm (NE), or mesoderm and endoderm (ME), characterized by lineage-specific transcriptional programs chromatin states. To date, the relationship between transcription factor activities dynamic changes that guide cell specification remains ill-defined. In this study, we employ mouse embryonic stem differentiation toward ME lineages to reveal crucial roles of Tbx Eomes globally establish enhancer accessibility as prerequisite for lineage competence ME-specific gene expression. EOMES cooperates with SWItch/sucrose non-fermentable (SWI/SNF) complex drive rewiring is essential overcome default NE differentiation, which favored asymmetries in at state. Following global remodeling, controlled additional signals such Wnt transforming growth β (TGF-β)/NODAL, a second layer expression regulation, can be mechanistically separated from initial remodeling activities.

Язык: Английский

Gastruloids: Pluripotent stem cell models of mammalian gastrulation and embryo engineering DOI Creative Commons
Alfonso Martínez Arias, Yusuke Marikawa, Naomi Moris

и другие.

Developmental Biology, Год журнала: 2022, Номер 488, С. 35 - 46

Опубликована: Май 7, 2022

Язык: Английский

Процитировано

47

A differentiation roadmap of murine placentation at single-cell resolution DOI Creative Commons
Xiangxiang Jiang, Yue Wang, Zhenyu Xiao

и другие.

Cell Discovery, Год журнала: 2023, Номер 9(1)

Опубликована: Март 17, 2023

The placenta is one of the most important yet least understood organs. Due to limitations conventional research approaches, we are still far from a comprehensive understanding mouse placentation, especially regarding differentiation trophoblast lineages at early developmental stage. To decipher cell compositions and processes, systematically profile single-cell transcriptomes cells extraembryonic tissues (embryonic day 7.5 (E7.5) E8.5) placentae (E9.5-E14.5) one-day intervals. We identify distinct types during including unreported progenitor intermediate precursor cells. An updated roadmap presented following systematic transcriptome analyses. Based on transcriptomic regulatory network inference, specify transcription factors responsible for regulation dynamic processes lineage diversification. map trajectories find that sinusoid giant arise subpopulation ectoplacental cone provide data resource shed light future mechanistic studies gene networks governing hemochorial placentation.

Язык: Английский

Процитировано

44

Modelling post-implantation human development to yolk sac blood emergence DOI Creative Commons
Joshua Hislop, Qi Song, Kamyar Keshavarz F.

и другие.

Nature, Год журнала: 2023, Номер 626(7998), С. 367 - 376

Опубликована: Дек. 13, 2023

Abstract Implantation of the human embryo begins a critical developmental stage that comprises profound events including axis formation, gastrulation and emergence haematopoietic system 1,2 . Our mechanistic knowledge this window life remains limited due to restricted access in vivo samples for both technical ethical reasons 3–5 Stem cell models have emerged help unlock mysteries 6–16 Here we present genetically inducible stem cell-derived embryoid model early post-implantation embryogenesis captures reciprocal codevelopment embryonic tissue extra-embryonic endoderm mesoderm niche with haematopoiesis. This is produced from induced pluripotent cells shows unanticipated self-organizing cellular programmes similar those occur embryogenesis, formation amniotic cavity bilaminar disc morphologies as well generation an anterior hypoblast pole posterior domain. The layer these embryoids lacks trophoblast advanced multilineage yolk sac tissue-like morphogenesis harbours process distinct waves haematopoiesis, erythroid-, megakaryocyte-, myeloid- lymphoid-like cells. presents easy-to-use, high-throughput, reproducible scalable platform probe multifaceted aspects development blood at stage. It will provide tractable human-based drug testing disease modelling.

Язык: Английский

Процитировано

33

Reconstructing axial progenitor field dynamics in mouse stem cell-derived embryoids DOI Creative Commons
Adriano Bolondi,

Benjamin K. Law,

Helene Kretzmer

и другие.

Developmental Cell, Год журнала: 2024, Номер 59(12), С. 1489 - 1505.e14

Опубликована: Апрель 4, 2024

Embryogenesis requires substantial coordination to translate genetic programs the collective behavior of differentiating cells, but understanding how cellular decisions control tissue morphology remains conceptually and technically challenging. Here, we combine continuous Cas9-based molecular recording with a mouse embryonic stem cell-based model trunk build single-cell phylogenies that describe transient, multipotent neuro-mesodermal progenitors (NMPs) as they commit into neural somitic cell types. We find NMPs show subtle transcriptional signatures related their recent differentiation contribute downstream lineages through surprisingly broad distribution individual fate outcomes. Although decision-making can be heavily influenced by environmental cues induce morphological phenotypes, axial intrinsically mature over developmental time favor lineage. Using these data, present an experimental analytical framework for exploring non-homeostatic dynamics transient progenitor populations shape complex tissues during critical windows.

Язык: Английский

Процитировано

18

Deep-Tissue Spatial Omics: Imaging Whole-Embryo Transcriptomics and Subcellular Structures at High Spatial Resolution DOI Creative Commons
Valentina Gandin, Jun Kim,

Liang-Zhong Yang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 17, 2024

Summary The inherent limitations of fluorescence microscopy, notably the restricted number color channels, have long constrained comprehensive spatial analysis in biological specimens. Here, we introduce cycleHCR technology that leverages multicycle DNA barcoding and Hybridization Chain Reaction (HCR) to surpass conventional barrier. facilitates high-specificity, single-shot imaging per target for RNA protein species within thick specimens, mitigating molecular crowding issues encountered with other imaging-based omics techniques. We demonstrate whole-mount transcriptomics 254 genes an E6.5∼7.0 mouse embryo, achieving precise three-dimensional gene expression cell fate mapping across a specimen depth ∼ 310 µm. Utilizing expansion microscopy alongside cycleHCR, unveil complex network 10 subcellular structures primary embryonic fibroblasts. Furthermore, hippocampal slice, image 8 targets profile transcriptome 120 genes, uncovering gradients cell-type specific nuclear structural variances. provides unifying framework multiplex imaging, offering quantitative solution elucidating regulations deep tissue contexts research potentially diagnostic applications.

Язык: Английский

Процитировано

11

Recording morphogen signals reveals mechanisms underlying gastruloid symmetry breaking DOI
Harold M. McNamara, Sabrina C. Solley, Britt Adamson

и другие.

Nature Cell Biology, Год журнала: 2024, Номер 26(11), С. 1832 - 1844

Опубликована: Окт. 2, 2024

Язык: Английский

Процитировано

11

Deep-tissue transcriptomics and subcellular imaging at high spatial resolution DOI
Valentina Gandin, Jun Kim,

Liang-Zhong Yang

и другие.

Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 20, 2025

Limited color channels in fluorescence microscopy have long constrained spatial analysis biological specimens. Here, we introduce cycle Hybridization Chain Reaction (HCR), a method that integrates multicycle DNA barcoding with HCR to overcome this limitation. cycleHCR enables highly multiplexed imaging of RNA and proteins using unified barcode system. Whole-embryo transcriptomics achieved precise three-dimensional gene expression cell fate mapping across specimen depth ~310 μm. When combined expansion microscopy, revealed an intricate network 10 subcellular structures mouse embryonic fibroblasts. In hippocampal slices, multiplex protein uncovered complex gradients cell-type-specific nuclear structural variations. provides quantitative framework for elucidating regulation deep tissue contexts research potentially diagnostic applications.

Язык: Английский

Процитировано

1

Epigenetic control of cell identities from epiblast to gastrulation DOI Creative Commons
Katrin M. Schüle, Simone Probst

FEBS Journal, Год журнала: 2025, Номер unknown

Опубликована: Фев. 22, 2025

Epigenetic modifications of chromatin are essential for the establishment cell identities during embryogenesis. Between embryonic days 3.5–7.5 murine development, major lineage decisions made that discriminate extraembryonic and tissues, primary germ layers formed, thereby laying down basic body plan. In this review, we cover contribution dynamic by DNA methylation, changes accessibility, histone modifications, in combination with transcription factors control gene expression programs different types. We highlight differences regulation enhancer promoter marks discuss their requirement specification. Importantly, many cases, lineage‐specific targeting epigenetic modifiers is carried out pioneer or master factors, sum mediate landscape cell‐type‐specific thus, identities.

Язык: Английский

Процитировано

1

The time has come to extend the 14-day limit DOI
Sophia McCully

Journal of Medical Ethics, Год журнала: 2021, Номер 47(12), С. e66 - e66

Опубликована: Фев. 2, 2021

For the past 40 years, 14-day rule has governed and, by defining a clear boundary, enabled embryo research and clinical benefits derived from this. It been both piece of legislation good practice globally. However, methods now allow embryos to be cultured for more than 14 days, something difficult imagine when was established, knowledge gained in intervening years provides robust scientific rationale why it is essential conduct on later stage human embryos. In this paper, I argue that current limit vitro should extended 28 days permit will illuminate our beginnings as well provide new therapeutic possibilities reduce miscarriage developmental abnormalities. also validation potentially useful alternatives. Through consideration ethical arguments, conclude there are no coherent or persuasive reasons deny researchers, through them humanity, innovation generate.

Язык: Английский

Процитировано

52

Rapid and efficient degradation of endogenous proteins in vivo identifies stage-specific roles of RNA Pol II pausing in mammalian development DOI Creative Commons
Abderhman Abuhashem, Andrew S. Lee, Alexandra L. Joyner

и другие.

Developmental Cell, Год журнала: 2022, Номер 57(8), С. 1068 - 1080.e6

Опубликована: Апрель 1, 2022

Язык: Английский

Процитировано

37