ORCID Profile
0000-0003-4375-7583
Current Organisations
Institut Curie
,
Centre National de la Recherche Scientifique
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Publisher: Elsevier BV
Date: 2021
Publisher: Cold Spring Harbor Laboratory
Date: 04-01-2021
DOI: 10.1101/2021.01.04.423386
Abstract: Triple-negative breast cancer is associated with the worst prognosis and the highest risk of recurrence among all breast cancer subtypes 1 . Residual disease, formed by cancer cells persistent to chemotherapy, remains one of the major clinical challenges towards full cure 2,3 . There is now consensus that non-genetic processes contribute to chemoresistance in various tumor types, notably through the initial emergence of a reversible chemotolerant state 4–6 . Understanding non-genetic tumor evolution stands now as a prerequisite for the design of relevant combinatorial approaches to delay recurrence. Here we show that the repressive histone mark H3K27me3 is a determinant of cell fate under chemotherapy exposure, monitoring epigenomes, transcriptomes and lineage with single-cell resolution. We identify a reservoir of persister basal cells with EMT markers and activated TGF-β pathway leading to multiple chemoresistance phenotypes. We demonstrate that, in unchallenged cells, H3K27 methylation is a lock to the expression program of persister cells. Promoters are primed with both H3K4me3 and H3K27me3, and removing H3K27me3 is sufficient for their transcriptional activation. Leveraging lineage barcoding, we show that depleting H3K27me3 alters tumor cell fate under chemotherapy insult – a wider variety of tumor cells tolerate chemotherapy. Our results highlight how chromatin landscapes shape the potential of unchallenged cancer cells to respond to therapeutic stress.
Publisher: Cold Spring Harbor Laboratory
Date: 22-07-2019
DOI: 10.1101/683037
Abstract: Assessing chromatin profiles at single-cell resolution is now feasible thanks to recently published experimental methods such as single cell chromatin immunoprecipitation followed by sequencing (scChIP-seq) (Grosselin et al., 2019 Rotem et al., 2015) and single-cell assay for transposase-accessibility chromatin (scATAC-seq) (Buenrostro et al., 2015 Chen et al., 2018 Cusanovich et al., 2015 Lareau et al., 2019). With these methods, we can detect the heterogeneity of epigenomic profiles within complex biological s les. Yet, existing tools used to analyze bulk epigenomic experiments are not fit for the low coverage and sparsity of single-cell epigenomic datasets. Here, we present ChromSCape: a user-friendly Shiny/R application that processes single-cell epigenomic data to help the biological interpretation of epigenomic landscapes within cell populations. The user can identify different sub-populations within heterogeneous s les, find differentially enriched regions between subpopulations and identify associated genes and pathways. ChromSCape accepts multiple s les to allow comparisons of cell populations between and within s les. ChromSCape source code is written in Shiny/R, works as a stand-alone application and is freely downloadable at allotlab/ChromSCape . Here, using ChromSCape on multiple H3K27me3 scChIP-seq datasets, we deconvolve chromatin landscapes within the tumor microenvironment, identifying distinct H3K27me3 landscapes associated to cell identity and tumor subtype. pacome.prompsy@curie.fr celine.vallot@curie.fr
Publisher: Springer Science and Business Media LLC
Date: 11-11-2020
DOI: 10.1038/S41467-020-19542-X
Abstract: Chromatin modifications orchestrate the dynamic regulation of gene expression during development and in disease. Bulk approaches have characterized the wide repertoire of histone modifications across cell types, detailing their role in shaping cell identity. However, these population-based methods do not capture cell-to-cell heterogeneity of chromatin landscapes, limiting our appreciation of the role of chromatin in dynamic biological processes. Recent technological developments enable the mapping of histone marks at single-cell resolution, opening up perspectives to characterize the heterogeneity of chromatin marks in complex biological systems over time. Yet, existing tools used to analyze bulk histone modifications profiles are not fit for the low coverage and sparsity of single-cell epigenomic datasets. Here, we present ChromSCape, a user-friendly interactive Shiny/R application distributed as a Bioconductor package, that processes single-cell epigenomic data to assist the biological interpretation of chromatin landscapes within cell populations. ChromSCape analyses the distribution of repressive and active histone modifications as well as chromatin accessibility landscapes from single-cell datasets. Using ChromSCape, we deconvolve chromatin landscapes within the tumor micro-environment, identifying distinct H3K27me3 landscapes associated with cell identity and breast tumor subtype.
Publisher: Springer Science and Business Media LLC
Date: 07-11-2018
DOI: 10.1007/S00253-018-9463-X
Abstract: Solid-state fermentation is a potential technology for developing lignocellulosic biomass-based biorefineries. This work dealt with solid-state fermentation for carboxylates production from corn stover, as building blocks for a lignocellulosic feedstock-based biorefinery. The effect of extrusion pretreatment, together with the action of a microbial consortia and hydrolytic enzymes as biotic triggers, was investigated on corn stover conversion, microbial metabolic pathways, and populations. The extrusion caused changes in the physical and morphological characteristics, without altering the biochemical composition of the corn stover. Extrusion also led to remarkable differences in the composition of the indigenous microbial population of the substrate. Consequently, it affected the structure of community developed after fermentation and the substrate conversion yield, which increased by 118% (from 23 ± 4 gCOD/kgVSi obtained with raw substrate to 51 ± 1 gCOD/kgVSi with extruded corn stover) with regard to self-fermentation experiments. The use of activated sludge as inoculum further increased the total substrate conversion into carboxylates, up to 60 ± 2 gCOD/kgVSi, and shaped the microbial communities (mainly composed of bacteria from the Clostridia and Bacteroidia classes) with subsequent homogenization of the fermentation pathways. The addition of hydrolytic enzymes into the reactors further increased the corn stover conversion, leading to a maximum yield of 142 ± 1 gCOD/kgVSi. Thus, extrusion pretreatment combined with the use of an inoculum and enzyme addition increased by 506% corn stover conversion into carboxylates. Beside biomass pretreatment, the results of this study indicated that biotic factor greatly impacted solid-state fermentation by shaping the microbial communities and related metabolic pathways.
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