Current topics in developmental biology/Current Topics in Developmental Biology, Год журнала: 2023, Номер unknown, С. 272 - 308
Опубликована: Дек. 6, 2023
Язык: Английский
Development, Год журнала: 2024, Номер 151(6)
Опубликована: Фев. 27, 2024
In the nascent mesoderm, TBXT expression must be precisely regulated to ensure that cells exit primitive streak and pattern anterior-posterior axis, but how varying dosage informs morphogenesis is not well understood. this study, we define transcriptional consequences of reduction during early human gastrulation using induced pluripotent stem cell models mesoderm differentiation. Multi-omic single-nucleus RNA ATAC sequencing 2D gastruloids comprising wild-type, heterozygous or null reveal does compromise ability a differentiate into instead directly influences temporal progression epithelial-to-mesenchymal transition with wild type transitioning first, followed by then null. By differentiating in monolayer format, further illustrate impacts persistence junctional proteins cell-cell adhesions. These results demonstrate can decoupled from acquisition mesodermal identity gastrula shed light on mechanisms underlying embryogenesis.
Язык: Английский
Процитировано
13
Nature Cell Biology, Год журнала: 2024, Номер 26(11), С. 1832 - 1844
Опубликована: Окт. 2, 2024
Язык: Английский
Процитировано
11
BioEssays, Год журнала: 2024, Номер 46(12)
Опубликована: Авг. 28, 2024
Abstract Gastrulation is a key milestone in the development of an organism. It period cell proliferation and coordinated cellular rearrangement, that creates outline body plan. Our current understanding mammalian gastrulation has been improved by embryo culture, but there are still many open questions difficult to address because intrauterine embryos low number specimens. In case humans, additional difficulties associated with technical ethical challenges. Over last few years, pluripotent stem models being developed have potential become useful tools understand gastrulation. Here we review these special emphasis on gastruloids provide survey methods produce them robustly, their uses, relationship embryos, prospects as well limitations.
Язык: Английский
Процитировано
8
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
Процитировано
7
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
Nature Communications, Год журнала: 2024, Номер 15(1)
Опубликована: Июнь 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
Язык: Английский
Процитировано
5
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Март 25, 2024
Micropatterned human pluripotent stem cells (hPSCs) treated with BMP4 (2D gastruloids) are among the most widely used cell models for gastrulation. Due to its simplicity and reproducibility, this system is ideal high throughput quantitative studies of tissue patterning has led many insights into mechanisms mammalian However, 2D gastruloids have only been studied up 48h. Here we extended 96h. We discovered a phase highly reproducible morphogenesis during which directed migration from primitive streak-like region gives rise mesodermal layer beneath an epiblast-like layer. Multiple types mesoderm arise striking spatial organization including lateral mesoderm-like on colony border paraxial further inside colony. Single transcriptomics showed strong similarity these in non-human primate embryos. our data suggest that annotation reference embryo may need be revised. This illustrates culture provides powerful model differentiation morphogenesis.
Язык: Английский
Процитировано
4
Nucleic Acids Research, Год журнала: 2025, Номер 53(3)
Опубликована: Янв. 24, 2025
Abstract Cell fate determination at the chromatin level is not fully comprehended. Here, we report that c-JUN acts on loci to limit mesoderm cell specification as cells exit pluripotency. Although widely expressed across various types in early embryogenesis, it essential for maintaining Instead, functions a repressor constrain development while having negligible impact ectoderm differentiation. interacts with MBD3–NuRD complex, which helps maintain low accessibility state mesoderm-related genes during differentiation of human pluripotent stem into mesoderm. Furthermore, specifically inhibits activation key factors, such EOMES and GATA4. Knocking out or inhibiting JNK inhibitor can alleviate this suppression, promoting Consistently, knockdown MBD3 enhances generation, whereas overexpression impedes it. Overexpressing redirects toward fibroblast-like lineage. Collectively, our findings suggest regulator restrict fate.
Язык: Английский
Процитировано
0
Nature Methods, Год журнала: 2025, Номер unknown
Опубликована: Май 7, 2025
Язык: Английский
Процитировано
0
BMC Genomics, Год журнала: 2025, Номер 26(1)
Опубликована: Май 8, 2025
Gastrulation represents a crucial stage in embryonic development and is tightly controlled by complex network involving epigenetic reprogramming. However, the molecular coordination among distinct layers entailing progressive restriction of lineage potency remains unclear. Here, we present multi-omics map H3K27ac H3K4me1 single-cell ChIP-seq profiles mouse embryos collected at six sequential time points. Significant priming, as reflected signals, evident, yet asynchronous cell fate commitment each germ layer histone modification levels are observed. Integrated scRNA-seq analysis unveil "time lag" transition pattern between enhancer activation gene expression during germ-layer specification. Notably, utilizing co-marked active enhancers, construct regulatory centered on pivotal transcription factors, highlighting potential critical role Cdkn1c mesoderm Together, our study broadens current understanding intricate networks governing gastrulation sheds light their relevance to congenital diseases.
Язык: Английский
Процитировано
0