Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neutral competition explains the clonal composition of neural organoids

ABSTRACT: Cerebral organoids model the development of the human brain and are an indispensable tool for studying neurodevelopment. Whole-organoid lineage tracing has revealed the number of progeny arising from each initial stem cell to be highly diverse, with lineage sizes ranging from one to more than 20,000 cells. This exceeds what can be explained by existing stochastic models of corticogenesis, indicating the existence of an additional source of stochasticity. We propose an explanation in terms of the SAN model in which this additional source of stochasticity is the survival time of a lineage within a long-lived population of symmetrically dividing cells under neutral competition. We demonstrate that this model explains the experimentally observed variability of lineage sizes and we derive a formula that captures the quantitative relationship between survival time and lineage size. Finally, we show that our model implies the existence of a regulatory mechanism to keeps the size of the symmetrically dividing cell population constant.

ORGANISM(S): Homo sapiens

PROVIDER: GSE255232 | GEO | 2024/03/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Cerebral organoids display dynamic clonal growth with lineage replenishment

Project description:During development tissue stem cells expand by symmetrical divisions while asymmetric divisions self-renew a tissue stem cell and produce differentiating cell types that assemble into functional organs. In brain development this process is variable for individual neural stem cells, resulting in differentially sized stem cell clones, but it is unclear how overall brain size is reproducibly generated during neurogenesis. Imaging-based lineage tracing allows for lineage analysis at high cellular resolution but systematic approaches to analyze clonal relationships in an entire tissue are currently lacking. Here we implement whole-tissue lineage tracing by genomic DNA barcoding in 3D human cerebral organoids and show that individual stem cell clones produce progeny on a vastly variable scale. We find that symmetrically dividing cells in a subpopulation of lineages continuously resides within the developing human tissue and drive the variable lineage size distribution. We show that stem cell output is tunable to tissue demands by chemical ablation or genetic fate restriction in chimeric organoids in which perturbed organoid development is completely compensated for by unaffected lineages. This data reveals adaptive plasticity of stem cell populations in developing human brain tissue dependent on tissue needs to ensure normal development.

2024-03-01 | GSE214105 | GEO

Metabolic lactate production coordinates vasculature development and progenitor behavior in the developing mouse neocortex

Project description:Proper neural progenitor behavior in conjunction with orderly vasculature formation is fundamental to the development of the neocortex. However, the mechanisms coordinating neural progenitor behavior and vessel growth remain largely elusive. Here we show that robust metabolic production of lactate by radial glial progenitors (RGPs) co-regulates vascular development and RGP division behavior in the developing mouse neocortex. RGPs undergo a highly organized lineage progression program to produce diverse neural progeny. Systematic single cell metabolic state analysis revealed that RGPs and their progeny exhibit distinct metabolic features associated with specific cell types and lineage progression statuses. Symmetrically dividing, proliferative RGPs preferentially express a cohort of genes that support glucose uptake and anaerobic glycolysis. Consequently, they consume glucose in anaerobic metabolism and produce a high level of lactate, which promotes vessel growth. Moreover, lactate production enhances RGP proliferation by maintaining mitochondrial length. Together, these results suggest that specific metabolic states and metabolites coordinately regulate vasculature formation and progenitor behavior in neocortical development.

2022-06-06 | GSE201991 | GEO

Mex3a Marks a Slowly Dividing Subpopulation of Lgr5+ Intestinal Stem Cells

Project description:The intestinal epithelium is continuously regenerated by highly proliferative Lgr5+ intestinal stem cells (ISCs). The existence of a population of quiescent ISCs has been suggested yet its identity and features remain controversial. Here we describe that the expression of the RNA-binding protein Mex3a labels a subpopulation of Lgr5+ cells that divide less frequently and contribute to regenerate all intestinal lineages with slow kinetics. Single cell transcriptomic analysis revealed two classes of Lgr5-high cells, one of them defined by the Mex3a-expression program and by low levels of proliferation genes. Lineage tracing experiments show that large fraction of Mex3a+ cell population is continuously recalled into the rapidly dividing self-renewing ISC pool in homeostatic conditions. Chemotherapy and radiation target preferentially rapidly dividing Lgr5+ cells but spare the Mex3a-high/Lgr5+ population, which helps sustain the renewal of the intestinal epithelium during treatment.

2017-03-14 | GSE90856 | GEO

Dynamic Optima In Cell Sizes Enable Normal Gastrulation Movements In Zebrafish Embryos During Early Development

Project description:Current knowledge of the mechanisms of cell migration is based on differentiated cells in culture where it is known that the actomyosin machinery drives migration via dynamic interactions with the extracellular matrix and adhesion complexes. However, unlike differentiated cells, cells in early metazoan embryos also dynamically change cell sizes as they migrate. The relevance of cell size to cell migration and embryonic development is not known. Here we investigate these phenomena in zebrafish embryos, a model system in which reductive cell divisions causes cell sizes to decrease naturally over time as cells migrate collectively to sculpt the embryonic body plan. Because mutations that can perturb cell sizes so early in development do not exist, we generate haploid and tetraploid zebrafish embryos and show that cell sizes in such embryos are smaller and larger than the diploid norm, respectively. Cells in embryos made of smaller or larger than normal cells migrate sub-optimally, leading to gastrulation defects. Multiple lines of evidence suggest that the observed defects originate from altered cell size, and not from pleotropic effects of altered ploidy. This interpretation is strengthened by finding that gastrulation defects are rescued by increasing cell sizes in embryos wherein cell sizes are smaller than normal. We show that the migration defects are cell-autonomous by live imaging migrating haploid and tetraploid cells during gastrulation in chimeric diploid embryos. Analysis of membrane protrusion dynamics in single cells shows that cells normally extend protrusions non-uniformly during migration, a phenomenon which is perturbed when cell sizes deviate from the norm. Thus, an optimal range of developmental stage-specific cell sizes appears necessary for collective cell migration to correctly position cells in space and time to shape an amorphous ball of blastoderm into an embryo.

2020-09-17 | GSE158023 | GEO

Expression data from Myotonic dystrophy type 1 (DM1) patient-derived induced pluripotent cell

Project description:DM1-iPSCs were generated from the peripheral blood of male adult patients. All clones were generated using episomal vectors. For skeletal muscle differentiation of the DM1-iPSCs, tet-on MYOD1 expression vector was transfected into DM1-iPSCs. To examine whether DM1-iPSC clones with different repeat sizes have acquired different characteristics, we isolated DM1-iPSC clones with different repeat sizes. We isolated 2 clones (S45 and S118) showing repeat size of 400~900, 2 clones (S14 and S24) showing repeat size of 1200~1600, and 2 clones (S1 and S16) showing repeat size of 1800~2800.

2024-12-16 | GSE214626 | GEO

The role of stochasticity in fungal community assembly – explaining apparent stochasticity by field experiments

Project description:Deadwood stochasticity

| PRJEB65750 | ENA

Centrosomal ALIX regulates mitotic spindle orientation by modulating astral microtubule dynamics

Project description:The orientation of the mitotic spindle (MS) is tightly regulated, but the molecular mechanisms are incompletely understood. Here we report a novel role for the multifunctional adaptor protein ALG-2-interacting protein X (ALIX) in regulating MS orientation in addition to its well-established role in cytokinesis. We show that ALIX is recruited to the pericentriolar material (PCM) of the centrosomes and promotes correct orientation of the MS in asymmetrically dividing Drosophila stem cells and epithelial cells, and symmetrically dividing Drosophila and human epithelial cells. ALIX-deprived cells display defective formation of astral microtubules (MTs), which results in abnormal MS orientation. Specifically, ALIX is recruited to the PCM via Drosophila Spindle defective 2 (DSpd-2)/Cep192, where ALIX promotes accumulation of g-tubulin and thus facilitates efficient nucleation of astral MTs. In addition, ALIX promotes MT stability by recruiting Microtubule Associated Protein 1S (MAP1S), which stabilizes newly formed MTs. Altogether, our results demonstrate a novel evolutionarily conserved role of ALIX in providing robustness to the orientation of the MS by promoting astral MT formation during asymmetric and symmetric cell division.

2018-06-04 | PXD009747 | Pride

Identification of genes with different expression in wild- and half-size Xenopus laevis embryos by transcriptome comparison

Project description:To identify genes with different expression levels in Xenopus laevis embryos of different sizes, RNAseq of middle gastrula RNA of the wild-size and artificially prepared half-size embryos was done. As a result, several genes with drastically different expression between these two types of embryos were found.

2020-09-29 | GSE158664 | GEO

Pathways identified by toxicogenomics analysis reveal the size and dose independency of silica particles-induced toxicity in mice.

Project description:Understanding the interactions of nanostructures with biological systems is essential to nanotoxicological research. Using a microarray-based toxicogenomics approach at early stage, this study investigated the relationship between particle size and toxicity of silica particles (SP) with diameters of 30, 70, and 300 nm (SP30, SP70, and SP300) as well as the mechanism of injury in mice. Two experiments with SiO2 particles of different sizes were considered in mice. One was aimed to investigate the dose-response relationship of SP70 toxicity at a dose of 10, 20, or 40 mg/kg (experiment 1), and the other set to study the size-response relationship of SP-induced toxicity using SP30, SP70, or SP300 (experiment 2). In experiment 2, two dosages each of SP30, SP70, and SP300 were performed. One was 10 mg/kg at three particle sizes, and the other was toxic doses of the three particle sizes, i.e., 10 mg/kg for SP30, 40 mg/kg for SP70, and 200 mg/kg for SP300. The toxic doses of the three particle sizes of SP were decided on the basis of the results of histopathological examinations and serum biochemical analysis in our previous study.n = 5

2011-07-31 | E-GEOD-30861 | biostudies-arrayexpress

Neutral evolution of snoRNA Host Gene long non-coding RNA affects cell fate control

Project description:A fundamental challenge in molecular biology is to understand how evolving genomes can acquire new functions. Several recent studies have underscored how non-conserved sequences can contribute to organismal diversification in the primate lineage. Actively transcribed, non-coding parts of the genome provide a potential platform for the development of new functional sequences, but their biological and evolutionary roles remain largely unexplored. Here we show that a set of neutrally evolving long non-coding RNAs (lncRNA) arising from small nucleolar RNA Host Genes (SNHGs) are highly expressed in skin and dysregulated in inflammatory conditions. Using SNHG7 and human epidermal keratinocytes as a model, we describe a mechanism by which these lncRNAs can increase self-renewal and inhibit differentiation. SNHG7 lncRNA’s activity has been acquired recently in the primate lineage and depends on a short sequence required for microRNA binding. Taken together, our results highlight the importance of understanding the role of fast-evolving transcripts in normal and diseased epithelia, and show how poorly conserved, actively transcribed non-coding sequences can participate in the evolution of genomic functionality.

2024-04-18 | GSE263910 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data