Identifying cross-lineage dependencies of cell-type specific regulators in gastruloids [ATAC-Seq]
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PROVIDER: PRJNA901376 | ENA |
REPOSITORIES: ENA
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Project description:Identifying cross-lineage dependencies of cell-type specific regulators in gastruloids
| PRJNA901372 | ENA
Project description:Identifying cross-lineage dependencies of cell-type specific regulators in gastruloids [scATAC-seq]
| PRJNA901379 | ENA
Project description:Correct gene expression levels in space and time are crucial for normal development. Advances in genomics enable the inference of gene regulatory programs that are active during development. However, this approach cannot capture the complex multicellular interactions that occur in embryogenesis. Compared to model organisms such as fruit flies and zebrafish, the growth of mammalian embryos in utero further complicates the analysis of cell-cell communication during development. However, in vitro models of mammalian development such as gastruloids allow to overcome this limitation. Using time-resolved single-cell chromatin accessibility analysis, we have delineated the regulatory landscape during gastruloid development and thereby identified the critical drivers of developmental transitions. We observed that gastruloids develop from pluripotent cells driven by the transcription factor (TF) dimer OCT4-SOX2 and differentiate along two main branches. A mesoderm branch driven by the TF MSGN1 and a spinal cord branch driven by CDX1, 2, 4 (CDX). Consistent with our lineage reconstruction, ΔCDX gastruloids fail to form spinal cord. Conversely, Msgn1 ablation inhibits the development of paraxial mesoderm, as expected. However, this also abolished spinal cord cells, which is surprising given that MSGN1 is not associated with differentiation along this branch. Therefore, formation of paraxial mesoderm is required for spinal cord development. To validate this, we generated chimeric gastruloids using ΔMSGN1 and wildtype cells, which formed both spinal cord and paraxial mesoderm. Strikingly, ΔMsgn1 cells specifically contributed to spinal cord, suggesting that cell-cell interactions between paraxial mesoderm and spinal cord are necessary for the formation the latter. Our work has important implications for the study of cell-cell communication in development and how the bridge can be made between gene regulatory programs and complex multicellular developmental structures.
2025-01-20 | GSE217905 | GEO
Project description:Correct gene expression levels in space and time are crucial for normal development. Advances in genomics enable the inference of gene regulatory programs that are active during development. However, this approach cannot capture the complex multicellular interactions that occur in embryogenesis. Compared to model organisms such as fruit flies and zebrafish, the growth of mammalian embryos in utero further complicates the analysis of cell-cell communication during development. However, in vitro models of mammalian development such as gastruloids allow to overcome this limitation. Using time-resolved single-cell chromatin accessibility analysis, we have delineated the regulatory landscape during gastruloid development and thereby identified the critical drivers of developmental transitions. We observed that gastruloids develop from pluripotent cells driven by the transcription factor (TF) dimer OCT4-SOX2 and differentiate along two main branches. A mesoderm branch driven by the TF MSGN1 and a spinal cord branch driven by CDX1, 2, 4 (CDX). Consistent with our lineage reconstruction, ΔCDX gastruloids fail to form spinal cord. Conversely, Msgn1 ablation inhibits the development of paraxial mesoderm, as expected. However, this also abolished spinal cord cells, which is surprising given that MSGN1 is not associated with differentiation along this branch. Therefore, formation of paraxial mesoderm is required for spinal cord development. To validate this, we generated chimeric gastruloids using ΔMSGN1 and wildtype cells, which formed both spinal cord and paraxial mesoderm. Strikingly, ΔMsgn1 cells specifically contributed to spinal cord, suggesting that cell-cell interactions between paraxial mesoderm and spinal cord are necessary for the formation the latter. Our work has important implications for the study of cell-cell communication in development and how the bridge can be made between gene regulatory programs and complex multicellular developmental structures.
2025-01-20 | GSE217903 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-01-20 | GSE217907 | GEO
Project description:Single cell transcriptomic study (using 10x Genomics v3 kits) of gastruloids, aggregates of mESCs, at different developmental timepoints (24h, 48h and 72h post-aggregation). mESCs, corresponding to the 0h timepoint, were also sequenced. The aim of this study was to delineate the cell state transition dynamics underlying anteroposterior symmetry breaking and germ layer formation in gastruloids. Gastruloids used in this study were generated from Bra::GFP reporter mESCs (Fehling et al., 2003).
2023-12-04 | E-MTAB-12749 | biostudies-arrayexpress
Project description:Identifying regulatory network governed by Candida albicans SREBP transcription regulators
| PRJNA485524 | ENA
Project description:Gastruloids are three-dimensional aggregates of embryonic stem cells (ESCs) that display key features of mammalian post-implantation development, including germ layer specification and axial organization. Gastruloids have mostly been characterized with microscopy-based approaches, limiting the number of genes that can be explored. It is therefore unclear to what extent gene expression in gastruloids reflects in vivo embryonic expression. Using both single-cell RNA-seq (scRNA-seq) and spatial transcriptomics we systematically compared cell types and spatial expression patterns between mouse gastruloids and mouse embryos.
2019-12-05 | GSE123187 | GEO
Project description:Gastruloids are a powerful in vitro model of early human development. However, although elongated and composed of all three germ layers, human gastruloids do not morphologically resemble post-implantation human embryos. Here we show that an early pulse of retinoic acid (RA), together with later Matrigel, robustly induces human gastruloids with posterior embryo-like morphological structures, including a neural tube flanked by segmented somites, and diverse cell types including neural crest, neural progenitors, renal progenitors, and myocytes. Through in silico staging based on single-cell RNA-seq (scRNA-seq), we find that human RA-gastruloids progress further than other human or mouse embryo models, aligning to E9.5 mouse and CS11 cynomolgus monkey embryos. We leverage chemical and genetic perturbations of RA-gastruloids to confirm that WNT and BMP signalling regulate somite formation and neural tube length in the human context, while transcription factors TBX6 and PAX3 underpin presomitic mesoderm and neural crest, respectively. Looking forward, RA-gastruloids are a robust, scalable model for decoding early human embryogenesis.
2024-06-20 | GSE208369 | GEO
Project description:Capturing cardiogenesis in gastruloids
| PRJNA667329 | ENA