Erythropoietin directly remodels the clonal composition of murine hematopoietic multipotent progenitor cells

Eisele, Almut; Cosgrove, Jason; Magniez, Aurélie; Tubeuf, Emilie; Bento, Sabrina Tenreira; Cayrac, Fanny; Tak, Tamar; Lyne, Anne-Marie; Urbanus, Jos; Perié, Leïla

doi:10.1101/2020.04.20.050146

Cited by 2 publications

(1 citation statement)

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“…3a). We leveraged our previous barcoding method 36 to allow robust detection of barcodes in scRNA-seq data, as shown by the high fraction of cells with a lineage barcode (Extended Fig. 3b).…”

Section: Textmentioning

confidence: 99%

H3K27me3 is a determinant of chemotolerance in triple-negative breast cancer

Marsolier

Prompsy

Durand

et al. 2021

Preprint

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SummaryTriple-negative breast cancer is associated with the worst prognosis and the highest risk of recurrence among all breast cancer subtypes1. Residual disease, formed by cancer cells persistent to chemotherapy, remains one of the major clinical challenges towards full cure2,3. There is now consensus that non-genetic processes contribute to chemoresistance in various tumor types, notably through the initial emergence of a reversible chemotolerant state4–6. 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.

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Section: Textmentioning

confidence: 99%

H3K27me3 is a determinant of chemotolerance in triple-negative breast cancer

Marsolier

Prompsy

Durand

et al. 2021

Preprint

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CellDestiny: A RShiny application for the visualization and analysis of single-cell lineage tracing data

et al. 2022

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Single-cell lineage tracing permits the labeling of individual cells with a heritable marker to follow the fate of each cell’s progeny. Over the last twenty years, several single-cell lineage tracing methods have emerged, enabling major discoveries in developmental biology, oncology and gene therapies. Analytical tools are needed to draw meaningful conclusions from lineage tracing measurements, which are characterized by high variability, sparsity and technical noise. However, the single cell lineage tracing field lacks versatile and easy-to-use tools for standardized and reproducible analyses, in particular tools accessible to biologists. Here we present CellDestiny, a RShiny app and associated web application developed for experimentalists without coding skills to perform visualization and analysis of single cell lineage-tracing datasets through a graphical user interface. We demonstrate the functionality of CellDestiny through the analysis of (i) lentiviral barcoding datasets of murine hematopoietic progenitors; (ii) published integration site data from Wiskott-Aldrich Symdrome patients undergoing gene-therapy treatment; and (iii) simultaneous barcoding and transcriptomic analysis of murine hematopoietic progenitor differentiation in vitro. In summary, CellDestiny is an easy-to-use and versatile toolkit that enables biologists to visualize and analyze single-cell lineage tracing data.

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Erythropoietin directly remodels the clonal composition of murine hematopoietic multipotent progenitor cells

Cited by 2 publications

References 93 publications

H3K27me3 is a determinant of chemotolerance in triple-negative breast cancer

H3K27me3 is a determinant of chemotolerance in triple-negative breast cancer

CellDestiny: A RShiny application for the visualization and analysis of single-cell lineage tracing data

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