Inflation-collapse dynamics drive patterning and morphogenesis in intestinal organoids
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA691471 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13415200.fastq.gz | Fastqsanger.gz | |||
| SRR13415201.fastq.gz | Fastqsanger.gz | |||
| SRR13415202.fastq.gz | Fastqsanger.gz | |||
| SRR13415203.fastq.gz | Fastqsanger.gz | |||
| SRR13415204.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 36 |
Similar Datasets
Project description:We apply single cell RNA-sequencing (scRNA-seq) to murine intestinal organoids in two experiments: 1) Comparing the transcriptomic landscape of organoids cultured in dome and sandwich culture systems (as described in the accompanying paper for this GEO submission), and 2) Assessing the transcriptomic landscape of organoids perturbed with CFTRinh-172 to inhibit inflation events, and with Forskolin to activate inflation events in the sandwich culture system, with respective controls. We find that the dome and sandwich culture systems produce similar abundance levels of each major specialized cell type, with similar marker gene expression shared across culture types. We find in the perturbation experiments a stretch-responsive cell state, similar in gene expression to several previously reported cell states, which is significantly more abundant in the Forskolin treated organoids compared to controls, and significantly less abundant in CFTRinh-172 treated organoids compared to controls. Additionally, we find that Stem and Enterocyte cell states are respectively, significantly less abundant, and more abundant in the Forskolin treated organoids compared to controls.
2021-01-13 | GSE164638 | GEO
Project description:How stem cells self-organize to form structured tissues is an unsolved problem. Intestinal organoids offer a model of self-organization as they generate stem cell zones (SCZs) of typical size even without a spatially structured environment. Here we examine processes governing the size of SCZs. We improve the viability and homogeneity of intestinal organoid cultures to enable long-term time-lapse imaging of multiple organoids in parallel. We find that SCZs are shaped by fission events under strong control of ion channel-mediated inflation and mechanosensitive Piezo-family channels. Fission occurs through stereotyped modes of dynamic behavior that differ in their coordination of budding and differentiation. Imaging and single-cell transcriptomics show that inflation drives acute stem cell differentiation and induces a stretch-responsive cell state characterized by large transcriptional changes, including upregulation of Piezo1. Our results reveal an intrinsic capacity of the intestinal epithelium to self-organize by modulating and then responding to its mechanical state.
| S-EPMC8419000 | biostudies-literature
Project description:Notch signaling is a core patterning module for vascular morphogenesis, which co-determines the sprouting behaviour of endothelial cells (ECs). Tight quantitative and temporal control of Notch activity is essential for vascular development, yet the details of Notch regulation in ECs are incompletely understood. We found that ubiquitin-specific peptidase 10 (USP10) interacted with the NOTCH1 intracellular domain (NICD1) to slow the ubiquitin-dependent turnover of this short-lived form of the activated NOTCH1 receptor. Accordingly, inactivation of USP10 reduced NICD1 abundance and stability, and diminished Notch-induced target gene expression in ECs. In mice, loss of endothelial Usp10 increased vessel sprouting and partially restored the patterning defects caused by ectopic expression of NICD1. Thus, USP10 functions as an NICD1 deubiquitinase, which fine-tunes endothelial Notch responses during angiogenic sprouting.
2019-04-11 | PXD013192 | Pride
Project description:Pigment patterns and skin appendages are prominent features of vertebrate skin. In zebrafish, regularly patterned pigment stripes and an array of calcified scales form simultaneously in the skin during post-embryonic development. Understanding mechanisms that regulate stripe patterning and scale morphogenesis may lead to discovery of fundamental mechanisms that govern development of animal form. To learn about cell types and potential signaling interactions that govern skin patterning and morphogenesis we generated and analyzed single cell transcriptomes of skin with genetic or induced defects in pigmentation and squamation. These data reveal a previously undescribed population of epidermal cells that express transcripts encoding enamel matrix proteins, suggest hormonal control of epithelial-mesenchymal signaling, clarify the signaling network that governs scale papillae development, and identify a critical role for the hypodermis in supporting pigment cell development. Additionally, this comprehensive single-cell transcriptome data from biomedically relevant skin conditions provide a useful resource to accelerate discovery of mechanisms governing skin development.
2023-06-16 | GSE224695 | GEO
Project description:Lumen formation and inflation are crucial for tubular organ morphogenesis, yet the underling mechanism remains largely unrevealed. Here, we applied 4D proteomics to screen the lumenogenesis-related proteins and reveal the potentially biological pathways that are involved in lumen inflation during notochord lumen formation in ascidian Ciona savignyi.
2023-05-10 | PXD037089 | Pride
Project description:Integrated in vitro models of human organogenesis are needed to elucidate the multi-systemic events underlying development and disease. We report the generation of human trunk-like structures that model the co-morphogenesis, patterning, and differentiation of the human spine and spinal cord. We identified differentiation conditions for human pluripotent stem cells favoring the formation of an embryo-like extending antero-posterior (AP) axis. Single cell and spatial transcriptomics show that somitic and spinal cord differentiation trajectories organize along this axis and can self-assemble into neural tubes surrounded by somites upon extracellular matrix addition. Morphogenesis is coupled with AP patterning mechanisms which results, at later stages of organogenesis, in in vivo-like arrays of neural subtypes along a neural tube surrounded by spine and muscle progenitors contacted by neuronal projections. This integrated system of trunk development indicates that in vivo-like multi-tissue morphogenesis and topographic organization of terminal cell types can be achieved in human organoids, opening windows for the development of more complex models of organogenesis.
2023-08-31 | GSE215982 | GEO
Project description:Integrated in vitro models of human organogenesis are needed to elucidate the multi-systemic events underlying development and disease. We report the generation of human trunk-like structures that model the co-morphogenesis, patterning, and differentiation of the human spine and spinal cord. We identified differentiation conditions for human pluripotent stem cells favoring the formation of an embryo-like extending antero-posterior (AP) axis. Single cell and spatial transcriptomics show that somitic and spinal cord differentiation trajectories organize along this axis and can self-assemble into neural tubes surrounded by somites upon extracellular matrix addition. Morphogenesis is coupled with AP patterning mechanisms which results, at later stages of organogenesis, in in vivo-like arrays of neural subtypes along a neural tube surrounded by spine and muscle progenitors contacted by neuronal projections. This integrated system of trunk development indicates that in vivo-like multi-tissue morphogenesis and topographic organization of terminal cell types can be achieved in human organoids, opening windows for the development of more complex models of organogenesis.
2023-08-31 | GSE215981 | GEO
Project description:Oriented cell divisions are critical for the formation and maintenance of structured epithelia. Proper mitotic spindle orientation relies on polarised anchoring of force generators to the cell cortex by the evolutionarily conserved Gαi-LGN-NuMA complex. However, the polarity cues that control cortical patterning of this ternary complex remain largely unknown in mammalian epithelia. Here we identify the membrane-associated protein Annexin A1 (ANXA1) as a novel interactor of LGN in mammary epithelial cells. ANXA1 acts independently of Gαi to instruct the accumulation of LGN and NuMA at the lateral cortex to ensure cortical anchoring of Dynein-Dynactin and astral microtubules and thereby planar alignment of the mitotic spindle. Loss of ANXA1 randomises mitotic spindle orientation, which in turn disrupts epithelial architecture and lumen formation in three-dimensional (3D) primary mammary organoids. Our findings establish ANXA1 as an upstream cortical cue that regulates LGN to direct planar cell divisions during mammalian epithelial morphogenesis.
2022-12-02 | PXD027452 | Pride
Project description:The goal of this study was to test the hypothesis that BMP signaling regulates patterning of human CDX2+ gut tube cultures (Spence et al 2011, Watson et al. 2014). The study is comprised of 2 separate experiments. The first experiment was to determine the immediate impact of BMP signaling on CDX2+ gut tube cultures. To do so we tested spheroids, spheroids after plating in Matrigel and exposed to 3 days of Noggin (100ng/mL), spheroids after plating in Matrigel and exposed to 3 days of EGF alone (100ng/mL, Control), and spheroids after plating in Matrigel and exposed to 3 days of BMP2 (100ng/mL). RNA was collected from spheroids and spheroids after 3 days of patterning. The second experiment examined if patterning was maintained after this initial 3 days of patterning and an addition 8-10 weeks following transplantation in vivo. To do this we grew all Matrigel plated spheroids for an additional 25 days in media containing EGF alone (Control media). We then transplanted these organoids under the mouse kidney capsule and allowed them to mature for 8-10 weeks. We then collected RNA from the transplanted organoids.
2017-04-20 | E-MTAB-5658 | biostudies-arrayexpress
Project description:There are on-going efforts to steer brain organoid development toward distinct regional identities by supplying cues in defined culture conditions. Here we incubated developing organoids with a number of patterning molecules at different concentrations to assess their effects on establishing brain region identities.
2021-02-11 | E-MTAB-10037 | biostudies-arrayexpress