Biology subjects

Jacquemin, G.

Publications and source records attributed to Jacquemin, G..

5 recordsLinked to original sources

bioRxiv2023

Leishmania infantum-exploited Nrf2 transcription factor as a virulence process to escape macrophage-driven ferroptosis-like leishmanicidal process

Macrophages are the main effector cells during Leishmania infection. They contribute to the detection and elimination of Leishmania spp. and may also promote parasite resilience. Here, we report that the activation of the transcription factor Nrf2 in macrophages plays a pivotal role in the progression of Leishmania infantum infection by controlling inflammation and redox balance of macrophages. We also highlight the involvement of NOX2/ROS axis in the early Nrf2 activation and subsequently of PGE2/EP2r signalling in the sustainment of Nrf2 activation upon L. infantum infection. Moreover, we establish macrophage-driven ferroptosis-like process as a cell death program of L. infantum and the protective effect of Nrf2 in macrophages against L. infantum death. Altogether, these results identify Nrf2 as a critical factor for the susceptibility of Leishmania infantum infection, highlighting Nrf2 as a promising pharmacological target for the development of new therapeutic approaches for the treatment of visceral leishmaniasis.

microbiology↗

bioRxiv2021

In vivo imaging of mammary epithelial cell dynamics in response to lineage-biased Wnt/Beta-catenin activation

Real-time, in vivo imaging provides an essential window into the spatiotemporal cellular and molecular events contributing to tissue development and pathology. By coupling longitudinal intravital imaging with genetic lineage tracing, here we captured the earliest cellular events underlying the impact of active Wnt/{beta}-catenin signaling on the organization and differentiation of the mammary epithelium. This enabled us to interrogate how Wnt/{beta}-catenin regulates the dynamics of distinct subpopulations of mammary epithelial cells in vivo and in real time. We show that {beta}-catenin stabilization, when targeted to either of the mammary luminal or basal epithelial lineages, invariably leads to cellular rearrangements that precipitate the formation of hyperplastic lesions that undergo squamous transdifferentiation. These results enhance our understanding of the earliest stages of hyperplastic lesion formation in vivo, and reveal that in mammary neoplastic development, {beta}-catenin activation dictates a hair-follicle/epidermal differentiation program independently of the targeted cell of origin.

cell biology↗

bioRxiv2021

Longitudinal high-resolution imaging through a flexible intravital imaging window

Intravital microscopy (IVM) is a powerful technique that enables imaging of internal tissues at (sub)cellular resolutions in living animals. Here, we present a silicone-based imaging window consisting of a fully flexible, suture-less design that is ideally suited for long-term, longitudinal IVM of growing tissues and tumors. Crucially, we show that this window, without any customization, is suitable for numerous anatomical locations in mice using a rapid and standardized implantation procedure. This low-cost device represents a substantial technological and performance advance that facilitates intravital imaging in diverse contexts in higher organisms, opening new avenues for in vivo imaging of soft and fragile tissues. One-sentence summaryThis study presents a versatile, fully flexible imaging window that acts as an implantable transparent second skin for small laboratory animal in vivo imaging.

cell biology↗

bioRxiv2020

Paracrine interactions between epithelial cells promote colon cancer growth

Tumours are complex ecosystems composed of different types of cells that communicate and influence each other. While the critical role of stromal cells in affecting tumour growth is well established, the impact of mutant cancer cells on healthy surrounding tissues remains poorly defined. Here, we uncovered a paracrine mechanism by which intestinal cancer cells reactivate foetal and regenerative Yap-associated transcriptional programs in neighbouring wildtype epithelial cells, rendering them adapted to thrive in the tumour context. We identified the glycoprotein Thrombospondin-1 (THBS1) as the essential factor that mediates non-cell autonomous morphological and transcriptional responses. Importantly, Thbs1 is associated with bad prognosis in several human cancers. This study reveals the THBS1-YAP axis as the mechanistic link mediating paracrine interactions between epithelial cells in intestinal tumours.

cancer biology↗

bioRxiv2018

Lineage tracing of Notch1-expressing cells in intestinal tumours reveals a distinct population of cancer stem cells.

Colon tumours are hierarchically organized and contain multipotent self-renewing cells, called Cancer Stem Cells (CSCs). We have previously shown that the Notch1 receptor is expressed in Intestinal Stem Cells (ISCs); given the critical role played by Notch signalling in promoting intestinal tumourigenesis, we explored Notch1 expression in tumours. Combining lineage tracing in two tumour models with transcriptomic analyses, we found that Notch1 + tumour cells are undifferentiated, proliferative and capable of indefinite self-renewal and of generating a heterogeneous clonal progeny. Molecularly, the transcriptional signature of Notch1+ tumour cells highly correlates with ISCs, suggestive of their origin from normal crypt cells. Surprisingly, Notch1+ expression labels a subset of CSCs that show reduced levels of Lgr5, a reported CSCs marker. The existence of distinct stem cell populations within intestinal tumours highlights the necessity of better understanding their hierarchy and behaviour, to identify the correct cellular targets for therapy.

cancer biology↗