Similar Datasets
Project description:Human cellular reprogramming to induced pluripotency is still an inefficient process, which has hindered studying the role of critical intermediate stages. Here we take advantage of high efficiency reprogramming in microfluidics and temporal multi-omics to identify and resolve distinct sub-populations and their interactions. We perform secretome analysis and single-cell transcriptomics to show functional extrinsic pathways of protein communication between reprogramming sub-populations and the re-shaping of a permissive extracellular environment. We pinpoint the HGF/MET/STAT3 axis as a potent enhancer of reprogramming, which acts via HGF accumulation within the confined system of microfluidics, and in conventional dishes needs to be supplied exogenously to enhance efficiency. Our data suggest that human cellular reprogramming is a transcription factor-driven process that it is deeply dependent on extracellular context and cell population determinants.
| S-EPMC10192362 | biostudies-literature
Project description:Each TMT6 sample contains one replicate with the sub-samples representing subsequent time points. Detailed culture and processing methods are described in Panariello et al, Nat Comm, under revision.
2022-12-22 | MSV000090954 | MassIVE
Project description:Cellular population dynamics shape the route to human pluripotency
| PRJNA915944 | ENA
Project description:After characterizing super-enhancer-associated chromatin dynamics accompanied by malignant progression of skin stem cells, we show that ETS family members auto-regulate themselves and a cohort of cancer-associated super-enhancer transcription factors which together are essential for tumor maintenance. Mouse skin squamouse cell carcinoma (SCC) tumor-initiating stem cells (SCC-SC), hair follicle stem cells (HF-SC) and epidermal stem cells (Epi-SC) were FACS-prufied for RNA-sequencing.
2015-11-22 | E-GEOD-72146 | biostudies-arrayexpress
Project description:Reprogramming to iPSCs resets the epigenome of somatic cells including the reversal of X chromosome-inactivation. We sought to gain insight into the steps underlying the reprogramming process by examining the means by which reprogramming leads to X chromosome-reactivation (XCR). Analyzing single cells in situ, we found that hallmarks of the inactive X (Xi) change sequentially, providing a direct readout of reprogramming progression. Several epigenetic changes on the Xi occur in the inverse order of developmental X-inactivation, while others are uncoupled from this sequence. Among the latter, DNA methylation has an extraordinary long persistence on the Xi during reprogramming, and, like Xist expression, is erased only after pluripotency genes are activated. Mechanistically, XCR requires both DNA demethylation and Xist silencing, ensuring that only cells undergoing faithful reprogramming initiate XCR. Our study defines the epigenetic state of multiple sequential reprogramming intermediates and establishes a paradigm for studying cell fate transitions during reprogramming. RRBS profiles were generated from female and male ES cells, female iPS cells, SSEA1+ and SSEA1- reprogramming intermediates, and male and female MEFs, for a total of 18 samples.
2014-12-18 | E-GEOD-58109 | biostudies-arrayexpress
Project description:Gene regulation in mammals involves a complex interplay between promoter and distal regulatory elements that function in concert to drive precise spatio-temporal gene expression programs. However, the dynamics of distal gene regulatory elements and its function in transcriptional reprogramming that underlies neurogenesis and neuronal activity remain largely unknown. Here we use a combinatorial analysis of genomewide datasets for chromatin accessibility (FAIRE-Seq) and enhancer mark H3K27ac to reveal a highly dynamic nature of chromatin accessibility during neurogenesis that gets restricted to certain genomic regions as neurons acquire a post-mitotic, terminally differentiated state. We further reveal that the distal open regions serve as target sites of distinct transcription factors that function in a stage-specific manner to contribute to the transcriptional program underlying neuronal commitment and maturation. A prolonged NMDA-driven neural activity results in epigenetic reprogramming at a large number of distal regulatory elements as well as dramatic reorganization of super-enhancers that in turn mediate critical transcriptional responses. Taken together, these findings reveal dynamics of distal regulatory landscape during neurogenesis and uncover novel regulatory elements that function in concert with epigenetic mechanisms and transcription factors to generate transcriptome underlying neuronal development and function. FAIRE-Seq and H3K27ac profiles for three stages on neuronal differentation viz. neuronal progenitors, day 1 neurons and day 10 neurons, were generated to understand the dynamics of accessible and ehancer chromatin landscape. Along with this we also generated RNASeq and H3K27ac profiles for day 10 neurons upon control and NMDA treatment.
2015-07-08 | E-GEOD-65713 | biostudies-arrayexpress
Project description:Quantitative in vivo cross-linking-mass spectrometry was used to identify significant time-dependent interactome changes that occur prior to large-scale proteome abundance remodeling in cells subjected to heat stress. Interactome changes were identified within minutes of applied heat stress, including changes in chaperone systems as expected due to altered functional demand. Global analysis of all interactome changes revealed the largest significant enrichment in the class of RNA binding proteins, providing new time-dependent conformational insight on complex relationships that exist between transcription, translation and cellular stress response mechanisms upstream of transcriptional reprogramming. Observed interactome dynamics of RNA binding proteins that are also HSP90 clients constitute mechanistic changes that increase HSP90 functional demand, evident from observed HSP90 interactome changes early in heat stress. However, these changes together with observed heat stress-induced ATP level reduction result in observed complex time-dependent HSP90 interactome dynamics, indicating HSP90 conformational bottleneck formation with increased stress duration.
2024-11-25 | PXD058191 | Pride
Project description:Lima1 is an extensively studied prognostic marker of malignancy and is also considered to be a tumour suppressor, but its role in a developmental context of non-transformed cells is poorly understood. Here, we characterise the expression pattern and examined the function of Lima1 in mouse embryos and pluripotent stem cell lines. We identify that Lima1 expression is controlled by the naïve pluripotency circuit and is required for the suppression of membrane blebbing, as well as for proper mitochondrial energetics in embryonic stem cells. Moreover, forcing Lima1 expression enables primed mouse and human pluripotent stem cells to be incorporated into murine pre-implantation embryos. Thus, Lima1 is a key effector molecule that mediates the pluripotency control of membrane dynamics and cellular metabolism.
| S-EPMC8807836 | biostudies-literature
Project description:Lima1 is an extensively studied prognostic marker of malignancy and is also considered to be a tumour suppressor, but its role in a developmental context of non-transformed cells is poorly understood. Here, we characterised the expression pattern and examined the function of Lima1 in mouse embryos and pluripotent stem cell lines. We found that Lima1 expression is controlled by the naïve pluripotency circuit and is required for the suppression of membrane blebbing. Moreover, Lima1 is essential for proper mitochondrial energetics, which is crucial for the growth of solid tumours. Forcing Lima1 expression enabled human pluripotent stem cells to be incorporated into murine pre-implantation embryos, trespassing the interspecies engraftment barrier. Thus, Lima1 is a key effector molecule that mediates the pluripotency control of membrane dynamics and cellular metabolism.
2021-12-16 | PXD025293 | Pride
Project description:My research project aims to use the clonal dynamics of spontaneously occurring somatic mutations to answer fundamental questions about human haematopoietic stem cell (HSC) biology.
The four major questions I will address are:
1. How do age and aging affect normal human HSC dynamics in vivo?
2. How do in vivo perturbations, particularly chemotherapy and increased levels of reactive oxygen species, affect HSC population dynamics?
3. Is response to in vitro perturbation heritable and/or correlated with other features such as age of individual and contribution of the lineage to peripheral blood?
4. How are HSC dynamics altered in people with early driver mutations (clonal haematopoiesis)?
| EGAS00001003397 | EGA