Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Memory sequencing reveals heritable single cell gene expression programs associated with distinct cellular behaviors

ABSTRACT: Non-genetic factors can cause individual cells to fluctuate substantially in gene expression levels over time. Yet it remains unclear whether these fluctuations can persist for much longer than the time of one cell division. Current methods for measuring gene expression in single cells mostly rely on single time point measurements, making the duration of gene expression fluctuations or cellular memory difficult to measure. Here, we report a method combining Luria and DelbrÃ¼ckâ€™s fluctuation analysis with population-based RNA sequencing (MemorySeq) for identifying genes transcriptome-wide whose fluctuations persist for several cell divisions. MemorySeq revealed multiple gene modules that are expressed together in rare cells within otherwise homogeneous clonal populations. Further, we found that these rare cell subpopulations are associated with biologically distinct behaviors, such as the ability to proliferate in the face of anti-cancer therapeutics, in different cancer cell lines. The identification of non-genetic, multigenerational fluctuations has the potential to reveal new forms of biological memory at the level of single cells and suggests that non-genetic heritability of cellular state may be a quantitative property

ORGANISM(S): Homo sapiens

PROVIDER: GSE151375 | GEO | 2020/05/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Synthetic circuits for tracking human cell fate

Project description:Cells respond heterogeneously to DNA damage. We engineered genetic circuits to detect differential responses in a population that persist for many days post-stimulus. We used microarrays to compare memory and non-memory subpopulations 3 days after DNA damage or doxycycline exposure. MD12/p53R2-RE and MD10/TetOx2 cells were either exposed to UV (10uJ/m^2) or doxycycline (1 ug/mL, 24 hours) and allowed to recover 3 days before sortng of memory and non-memory cells and RNA extraction. Two replicates were submitted for each condition (UV memory, UV non-memory, dox memory, dox non-memory)

2012-05-23 | E-GEOD-38189 | biostudies-arrayexpress

Disrupting cellular memory to overcome drug resistance

Project description:Plasticity enables cells to change their gene expression state in the absence of a genetic change. At the single-cell level, these gene expression states can persist for different lengths of time which is a quantitative measurement referred to as gene expression memory. Because plasticity is not encoded by genetic changes, these cell states can be reversible, and therefore, are amenable to modulation by disrupting gene expression memory. However, we currently do not have robust methods to find the regulators of memory or to track state switching in plastic cell populations. Here, we developed a lineage tracing-based technique to quantify gene expression memory and to identify single cells as they undergo cell state transitions. Applied to human melanoma cells, we quantified long-lived fluctuations in gene expression that underlie resistance to targeted therapy. Further, we identified the PI3K and TGF-β pathways as modulators of these state dynamics. Applying the gene expression signatures derived from this technique, we find that these expression states are generalizable to in vivo models and present in scRNA-seq from patient tumors. Leveraging the PI3K and TGF-β pathways as dials on memory between plastic states, we propose a "pretreatment" model in which we first use a PI3K inhibitor to modulate the expression states of the cell population and then apply targeted therapy. This plasticity informed dosing scheme ultimately yields fewer resistant colonies than targeted therapy alone. Taken together, we describe a technique to find modulators of gene expression memory and then apply this knowledge to alter plastic cell states and their connected cell fates.

2023-09-29 | GSE237228 | GEO

Synthetic circuits for tracking human cell fate

2012-05-24 | GSE38189 | GEO

Multigenerational effect of heat stress on the Drosophila melanogaster sperm proteome

Project description:The notion that genes are the sole units of heredity and that a barrier exists between soma and germline has been a major hurdle in elucidating the heritability of traits that were observed to follow a non-Mendelian inheritance pattern. It was only after the conception of “epigenetics” by C. H. Waddington that the effect of parental environment on subsequent generations via non-DNA sequence-based mechanisms, such as DNA methylation, chromatin modifications, non-coding RNAs and proteins, could be established in various organisms, now referred to as multigenerational epigenetic inheritance. Despite the growing body of evidence, the male gamete-derived epigenetic factors that mediate the transmission of such phenotypes are seldom explored, particularly in the model organism Drosophila melanogaster. Using the heat stress-induced multigenerational epigenetic inheritance paradigm in a widely used position-effect variegation line of Drosophila, named white-mottled, we have dissected the effect of heat stress on the sperm proteome in the current study. We demonstrate that multiple successive generations of heat stress at the early embryonic stage results in a significant downregulation of proteins associated with translation, chromatin organization, microtubule-based processes, and generation of metabolites and energy in the Drosophila sperms. Based on our findings, we propose chromatin-based epigenetic mechanisms, a well-established mechanism for environmentally induced multigenerational effects, as a plausible way of transmitting heat stress memory via the male germ line in subsequent generations. Moreover, we demonstrate the effect of multiple generations of heat stress on the reproductive fitness of Drosophila, shedding light on the adaptive or maladaptive potential of heat stress-induced multigenerational phenotypes.

2024-05-10 | PXD037488 | Pride

Synthetic circuit identifies subpopulations with sustained memory of DNA damage

Project description:Differential responses to stimuli can affect how cells succumb to disease. In yeast, DNA damage can create heterogeneous responses. To delineate how a response contributes to a cell's future behavior, we constructed a transcription-based memory circuit that detects DNA repair to isolate subpopulations with heritable damage responses. Strongly responsive cells show multigenerational effects, including growth defects and iron-associated gene expression. Less-responsive cells exhibit increased mutation frequencies but resume wild-type behavior. These two subpopulations remain distinct for multiple generations, indicating a transmissible memory of damage. Collectively, this work demonstrates the efficacy of using synthetic biology to define how environmental exposure contributes to distinct cell fates. Cells containing the HUG1 memory device (Burrill, 2011) were exposed to 0.3% EMS for 24 h and recovered for 36 h, at which point cells were sorted based on YFP expression, i.e. memory and non-memory cells. These two sorted populations were then grown for another 12 h, at which point transcriptional profiling was performed.

2012-03-02 | E-GEOD-36210 | biostudies-arrayexpress

piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans

Project description:Transgenerational effects likely have wide-ranging implications for human health, biological adaptation and evolution, however their mechanism and biology remain poorly understood. Here we demonstrate that a germline nuclear small RNA/chromatin pathway can maintain epi-allelic inheritance for many generations when triggered by a piRNA-dependent foreign RNA response in C. elegans. Using forward genetic screens and candidate approaches we find that a core set of nuclear RNAi and chromatin factors are required for multigenerational inheritance of environmental RNAi and piRNA silencing. These include a germline-specific nuclear Argonaute HRDE1/WAGO-9, a HP1 otholog HPL-2 and two putative histone methyltransferases, SET-25 and SET-32. Most surprisingly, piRNAs can trigger highly stable long-term silencing lasting at least 20 generations. Once established, this long-term memory becomes independent of the piRNA trigger but remains dependent on the nuclear RNAi/chromatin pathway. Our data present the first report of multigenerational epigenetic inheritance induced by piRNAs in any organism. Seven C. elegans small RNA libraries from three distinct experiments (A, B, C) were sequenced using Illumina sequencing technology. Five small RNA libraries were prepared according to library construction protocol 1 and sequenced as part of 22 flow cell lanes on the Illumina GA IIx platform. Samples were labelled for multiplexing using 4-bp 5'-barcodes, a single flow cell lane included several multiplexed libraries. Two small RNA libraries were prepared according to library construction protocol 2 and sequenced on the Illumina MiSeq platform.

2012-06-25 | E-GEOD-38813 | biostudies-arrayexpress

Arabidopsis diurnal LFQ proteome and labelled phosphoproteome

Project description:Plant growth and survival depends to a large extent on the diurnal regulation of cellular processes. Although extensively studied at the transcript level, notably less is known about diurnal fluctuations at the protein level. Here, we report a high-resolution quantitative time-course of the Arabidopsis rosette proteome and phosphoproteome over a 12 h light:12 h dark diel cycle. We monitored the proteome every 2 h and the phosphoproteome immediately before and after the light-to-dark and dark-to-light transitions. Notably, we quantified nearly 5000 proteins and 1800 phosphopeptides, of which 288 and 225, respectively, were found to fluctuate over the time-course. Diurnal proteome and phosphoproteome changes were related to diverse biological processes, including protein translation, light detection, photosynthesis, metabolism and transport. Together, these datasets represent the most comprehensive proteomic analysis of Arabidopsis rosettes to date, allowing us to make multi-level inferences about the diurnal regulation of key cellular plant processes plants.

2020-12-18 | PXD007600 | Pride

Multigenerational effect of antibiotic tetracycline on transcriptional responses of D. magna and its relationship to higher levels of biological organizations

Project description:Given the risk of environmental pollution by pharmaceutical compounds and the effects of these compounds on exposed ecosystems, ecologically relevant and realistic assessments are required. However, many studies have been mostly focused on individual responses in a single generation exposed to one-effect concentration. Here, transcriptional responses of the crustacean Daphnia magna to the antibiotic tetracycline across multiple generations and effect concentrations were investigated. The results demonstrated that tetracycline induced different transcriptional responses of daphnids that were dependent on dose and generation. For example, reproduction-related expressed sequence tags (ESTs), including vitellogenin, were distinctly related to the dose-dependent tetracycline exposure, whereas multigenerational exposure induced significant change of molting-related ESTs such as cuticle protein. Sixty-five ESTs were shared in all contrasts, suggesting a conserved mechanism of tetracycline toxicity regardless of exposure concentration or time. Most of them were associated with general stress responses including translation, protein and carbohydrate metabolism, and oxidative phosphorylation. In addition, effects across the dose-response curve showed higher correlative connections among transcriptional, physiological, and individual responses than multigenerational effects. In the multigenerational exposure, the connectivity between adjacent generations decreased with increasing generation number. The results clearly highlight that exposure concentration and time trigger different mechanisms and functions, providing further evidence that multigenerational and dose-response effects cannot be neglected in environmental risk assessment.

2017-10-16 | GSE94439 | GEO

piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans

2012-06-25 | GSE38813 | GEO

The immunopathological landscape of human pre-TCRα deficiency: from rare to common variants

Project description:We report humans with biallelic loss-of-function PTCRA rare variants impairing pre-TCR-⍺ expression. Low naive ⍺β T cell blood counts at birth persist over time with normal memory ⍺β and high γδ T cell counts. Early productive TCR-δ or TCR-⍺ rearrangements can rescue ⍺β T cell differentiation by stabilizing low levels of cell surface CD3. Only a minority of them are sick, with infection, lymphoproliferation, and/or autoimmunity. We also report that ~1/4,000 individuals from the Middle East and South Asia are homozygous for a hypomorphic PTCRA common variant. They have normal naive ⍺β T cell but high γδ T cell blood counts. Residual expression of their pre-TCR-⍺ enables differentiation of more ⍺β T cells. However, these patients have autoimmune conditions more commonly than the general population.

2024-02-14 | GSE243927 | 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