Biology subjects

Marsolier, J.

Publications and source records attributed to Marsolier, J..

3 recordsLinked to original sources

bioRxiv2026

Matched single-cell chromatin, transcriptome, and surface marker profiling captures in vivo epigenomic reprogramming during basal-to-luminal transition in the mammary gland

Single-cell multi-omics methods enable simultaneous mapping of chromatin states and transcriptomes, offering deep insights into gene regulation. Yet, the full potential of these approaches remains untapped for rare cell populations, as most methods require thousands of cells and are limited in their ability to capture multiple molecular layers comprehensively within the same cell. Here, we introduce OneCell CUT&Tag a user-friendly method that provides matched high-resolution epigenome, full-transcriptome, and surface marker quantification from every cell, with input as low as one cell. Using this approach, we uncovered epigenomic priming of basal cells in the mammary gland and captured the dynamics of basal-to-luminal transdifferentiation. We identified a transitional cell population with intermediate epigenomic profiles--absent in reference populations--and demonstrated a continuous epigenomic progression from basal to luminal states, while transcriptomes exhibited a binary switch. Adaptable to diverse samples and tissues, this method also revealed the role of H3K27me3 in shaping zygotic expression programs. By matching multiple layers of molecular information at single-cell resolution, OneCell CUT&Tag dissects the complementary roles of each omics layer in shaping cellular identity and function, opening new avenues to study rare and complex biological systems.

genomics↗

bioRxiv2025

Identification of a shared persistence program in triple-negative breast cancer across treatments and patients

Acquisition of resistance to anti-cancer therapies is a multistep process, which initiates with the survival of drug persister cells. Understanding the mechanisms driving the emergence of persister cells remains challenging, primarily because of their limited accessibility in patients. Here, using mouse models to isolate persister cells from patient tumors, we determine the identity features of persister cells from eight patients with triple-negative breast cancer (TNBC). Combining over 80 transcriptome studies, we reveal hallmarks of the persister state across patient models and treatment modalities: high expression of basal keratins together with activation of a stress response and inflammation pathways. Patient-derived persister cells are transcriptionally plastic and return to a common treatment-naive like state upon relapse, regardless of the treatment they have been exposed to. Leveraging gene regulatory networks, we identify AP-1, NFKB and IRF/STAT as the key drivers of this hallmark persister state. As a proof of concept, we show that FOSL1 - an AP-1 member - is sufficient to drive cells to the persister state by binding enhancers and reprogramming the transcriptome of cancer cells. On the contrary, cancer cells without FOSL1 have a decreased ability to reach the persister state. By defining hallmarks of drug persistence to multiple therapies of the standard of care, our study provides a resource to design novel combination therapeutic strategies to limit resistance.

cancer biology↗

bioRxiv2021

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

Triple-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-{beta} 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.

cancer biology↗