Visualization of individual cell division history in complex tissues
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ABSTRACT:
PROVIDER: PRJNA704410 | ENA |
REPOSITORIES: ENA
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Project description:The division potential of individual stem cells and the molecular consequences of successive rounds of proliferation remain largely unknown. Here, we developed an inducible cell division counter (iCOUNT) that reports cell division events in human and mouse tissues in vitro and in vivo. Analysing cell division histories of neural stem/progenitor cells (NSPCs) in the developing and adult brain, we show that iCOUNT can provide novel insights into stem cell behaviour. Further, we used single cell RNA-sequencing (scRNA-seq) of iCOUNT-labelled NSPCs and their progenies from the developing mouse cortex and forebrain-regionalized human organoids to identify molecular pathways that are commonly regulated between mouse and human cells, depending on individual cell division histories. Thus, we developed a novel tool to characterize the molecular consequences of repeated cell divisions of stem cells that allows an analysis of the cellular principles underlying tissue formation, homeostasis, and repair.
2021-07-19 | GSE167375 | GEO
Project description:The division potential of individual stem cells and the molecular consequences of successive rounds of proliferation remain largely unknown. Here, we developed an inducible cell division counter (iCOUNT) that reports cell division events in human and mouse tissues in vitro and in vivo. Analyzing cell division histories of neural stem/progenitor cells (NSPCs) in the developing and adult brain, we show that iCOUNT can provide novel insights into stem cell behavior. Further, we use single-cell RNA sequencing (scRNA-seq) of iCOUNT-labeled NSPCs and their progenies from the developing mouse cortex and forebrain-regionalized human organoids to identify functionally relevant molecular pathways that are commonly regulated between mouse and human cells, depending on individual cell division histories. Thus, we developed a tool to characterize the molecular consequences of repeated cell divisions of stem cells that allows an analysis of the cellular principles underlying tissue formation, homeostasis, and repair.
| S-EPMC8577829 | biostudies-literature
Project description:The numerous neurons and glia that form the brain originate from tightly controlled growth and division of neural stem cells, regulated systemically by known extrinsic signals. However, the intrinsic mechanisms that control the characteristic proliferation rates of individual neural stem cells are unknown. Here, we show that the size and division rates of Drosophila neural stem cells (neuroblasts) are controlled by the highly conserved RNA binding protein Imp (IGF2BP), via one of its top binding targets in the brain, myc mRNA. We show that Imp stabilises myc mRNA leading to increased Myc protein levels, larger neuroblasts, and faster division rates. Declining Imp levels throughout development limit myc mRNA stability to restrain neuroblast growth and division, while heterogeneous Imp expression correlates with myc mRNA stability between individual neuroblasts in the brain. We propose that Imp-dependent regulation of myc mRNA stability fine-tunes individual neural stem cell proliferation rates.
2020-02-05 | GSE140704 | GEO
Project description:To validate whether division history is linked to functional and transcriptional properties we established a CTV-based serial-transfer approach that allowes single cell transcriptional profiling of memory T cells that have undergone a high or low amount of prior division
2022-01-31 | GSE184947 | GEO
Project description:Just as animal monozygotic twins can experience different environmental conditions by being reared apart, individual genetically-identical trees of the genus Populus can also be exposed to contrasting environmental conditions by being grown in different locations. As such, clonally-propagated Populus trees provide an opportunity to interrogate the impact of individual environmental history on current response to environmental stimuli. To test the hypothesis that current responses to an environmental stimulus, drought, are contingent on environmental history, the transcriptome-level drought responses of three economically important hybrid genotypes: DN34 (Populus deltoides x P. nigra); Walker (P. deltoides var. occidentalis x (P. laurifolia x P. nigra)); and, Okanese (‘Walker’ x (P. laurifolia x P. nigra)) derived from two different locations were compared. Strikingly, differences in transcript abundance patterns in response to drought were based on differences in geographic origin of clones for two of the three genotypes. This observation was most pronounced for the genotypes with the longest time since establishment and last common propagation. Differences in genome-wide DNA methylation paralleled the transcriptome level trends, where the clones with the most divergent transcriptomes and clone history had the most marked differences in the extent of total DNA methylation, suggesting an epigenetic basis for the clone-history-dependent transcriptome divergence. The data provide insights into the interplay between genotype and environment in the ecologically and economically important Populus genus, with implications for both the industrial application of Populus trees, and the evolution and persistence of these important tree species.
2011-05-01 | GSE27693 | GEO
Project description:Just as animal monozygotic twins can experience different environmental conditions by being reared apart, individual genetically-identical trees of the genus Populus can also be exposed to contrasting environmental conditions by being grown in different locations. As such, clonally-propagated Populus trees provide an opportunity to interrogate the impact of individual environmental history on current response to environmental stimuli. To test the hypothesis that current responses to an environmental stimulus, drought, are contingent on environmental history, the transcriptome-level drought responses of three economically important hybrid genotypes: DN34 (Populus deltoides x P. nigra); Walker (P. deltoides var. occidentalis x (P. laurifolia x P. nigra)); and, Okanese (‘Walker’ x (P. laurifolia x P. nigra)) derived from two different locations were compared. Strikingly, differences in transcript abundance patterns in response to drought were based on differences in geographic origin of clones for two of the three genotypes. This observation was most pronounced for the genotypes with the longest time since establishment and last common propagation. Differences in genome-wide DNA methylation paralleled the transcriptome level trends, where the clones with the most divergent transcriptomes and clone history had the most marked differences in the extent of total DNA methylation, suggesting an epigenetic basis for the clone-history-dependent transcriptome divergence. The data provide insights into the interplay between genotype and environment in the ecologically and economically important Populus genus, with implications for both the industrial application of Populus trees, and the evolution and persistence of these important tree species. 72 arrays total. 2 time points. 2 water regimes. 3 biological replicates per treatment
2011-05-01 | E-GEOD-27693 | biostudies-arrayexpress
Project description:Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability
| PRJNA591594 | ENA
Project description:Chromatin accessibility in the nucleus is a predictor of gene expression, cell division and cell type specificity. NicE-viewSeq (Nicking Enzyme assisted viewing and Sequencing) allows accessible chromatin visualization and sequencing with lower mitochondrial DNA and duplicated sequences compared to ATACsee. Using NicE-viewSeq we interrogated cell cycle G1, S and G2M specific accessible chromatin in mammalian cells. Despite DNA replication and subsequent condensation of chromatin to chromosome, chromatin accessibility remained subtly altered and generally preserved. Genome-wide alteration of accessibility for TSS and enhancer gradually decreased as the cell progressed from G1 to G2M, with distinctive differential accessibility near consensus transcription factors sites. Inhibition of histone deacetylase promoted accessible chromatin of the gene body, correlating with apoptotic gene expression. In addition, reduced chromatin accessibility for MYC oncogene pathway correlated with gene down regulation. Surprisingly, repetitive RNA expression remained unaltered following histone acetylation mediated increased accessibility. Therefore, we suggest that subtle changes in chromatin accessibility is a prerequisite during cell cycle and histone deacetylase inhibitor mediated therapeutics.
2020-09-09 | GSE139253 | GEO
Project description:The history of click-speaking Khoe-San, and African populations in general, remains poorly understood. We genotyped ~2.3 million SNPs in 220 southern Africans and found that the Khoe-San diverged from other populations at least 100,000 years ago, but structure within the Khoe-San dated back to about 35,000 years ago. Genetic variation in various sub-Saharan populations did not localize the origin of modern humans to a single geographic region within Africa, instead, it indicated a history of admixture and stratification. We found evidence of adaptation targeting muscle function and immune response, potential adaptive introgression of UV-light protection, and selection predating modern human diversification involving skeletal and neurological development. These new findings illustrate the importance of African genomic diversity in understanding human evolutionary history .220 samples were analysed with the Illumina HumanOmni2.5-Quad BeadChip and are described herein.
2012-09-22 | E-MTAB-1259 | biostudies-arrayexpress