Biology subjects

Saintpierre, B.

Publications and source records attributed to Saintpierre, B..

5 recordsLinked to original sources

bioRxiv2026

Monocytes promote intraepithelial infiltration of effector memory CD8+ T cells in regressing tumors

Despite the clinical success of cancer immunotherapies, the cellular interactions driving tumor regression remain incompletely understood. Here, we investigated the dynamic remodeling of the tumor immune microenvironment during regression of transplanted PyMT mammary tumors following STING agonist treatment. Using scRNA-seq of sorted CD8+ T cells and myeloid cells, combined with imaging approaches, we identified major changes in both lymphoid and myeloid compartments during tumor regression. Regressing tumors showed a transient accumulation of Ly6Chi monocyte populations associated with a decline in macrophage subsets, while effector and memory CD8+ T-cell populations increased at the expense of exhausted T cells. Interaction analyses predicted enhanced chemotactic and adhesion interactions between CXCL9+ Ly6Chi monocytes and effector CD8+ T cells. Consistently, dynamic imaging revealed increased CD8+ T-cell motility and infiltration into tumor cores following treatment. In particular, CXCR6+ effector CD8+ T cells transiently accumulated within tumor islets during regression before relocalizing to stromal regions. Together, these findings reveal a coordinated spatiotemporal remodeling of myeloid and CD8+ T-cell populations during immunotherapy-induced tumor regression and highlight cooperative interactions that may promote durable anti-tumor immunity.

immunology↗

bioRxiv2025

Spatial and Multiomic profiling of muscle regeneration dynamics in Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a pediatric degenerative myopathy caused by the absence of functional dystrophin. As a result, DMD muscles exhibit compromised myofiber integrity and increased susceptibility to mechanical damage. In early disease stages, muscles undergo repeated cycles of degeneration and regeneration; over time, however, this regenerative capacity declines, leading to the gradual replacement of muscle tissue with fat and fibrosis. While several signaling pathways have been identified as deregulated in dystrophic muscle, the cellular and molecular mechanisms underlying this regenerative exhaustion remain to be fully elucidated. To address this, we constructed a comprehensive cellular atlas of human dystrophic muscle using high-resolution spatial transcriptomics (Visium HD), capturing the cellular crosstalk within regenerative regions. Cell-to-cell communication analysis revealed activation of Notch signaling mediated by NOTCH3 in activated satellite cells. Immunostaining confirmed elevated NOTCH3 expression in both DMD patient samples and in the mdx mouse model at late disease stages. Silencing of NOTCH3 in primary myoblasts improved myogenic differentiation, pinpointing NOTCH3-mediated signaling as a contributor to regeneration impairment. To further dissect the dynamics of regeneration and infer the gene regulatory networks governing myogenic differentiation, we integrated paired snRNA-seq and snATAC-seq data from young, adult, and aged mdx mice. This analysis identified GLIS3 upregulation as an additional barrier to effective myogenesis. GLIS3 displayed an overall increase in dystrophic muscles, while silencing experiments enhanced differentiation in myoblasts. Together, our work reveals intrinsic defects in the dystrophic stem cell compartment that emerge during disease progression and hinder the execution of the myogenic program. These findings suggest NOTCH3 and GLIS3 as potential therapeutic targets to enhance regeneration and maintain muscle integrity in DMD. This study provides a high-resolution map of the dystrophic regenerative landscape and offers a valuable resource for future translational research.

cell biology↗

bioRxiv2023

Pancreatic islet cell stress induced by insulin-degrading enzyme deficiency promotes islet regeneration and protection from autoimmune diabetes

Appropriate tuning of protein homeostasis through mobilization of the unfolded protein response (UPR) is key to the capacity of pancreatic beta cells to cope with highly variable demand for insulin synthesis. An efficient UPR ensures a sufficient beta cell mass and secretory output but can also affect beta cell resilience to autoimmune aggression. The factors regulating protein homeostasis in the face of metabolic and immune challenges are insufficiently understood. We examined beta cell adaptation to stress in mice deficient for insulin-degrading enzyme (IDE), a ubiquitous protease with high affinity for insulin and genetic association with type 2 diabetes. IDE deficiency induced a low-level UPR in both C57BL/6 and autoimmune non-obese diabetic (NOD) mice, associated with rapamycin-sensitive beta cell proliferation strongly enhanced by proteotoxic stress. Moreover, in NOD mice, IDE deficiency protected from spontaneous diabetes and triggered an additional independent pathway, conditional on the presence of islet inflammation but inhibited by proteotoxic stress, highlighted by strong upregulation of regenerating islet-derived protein 2, a protein attenuating autoimmune inflammation. Our findings establish a key role of IDE in islet cell protein homeostasis, identify a link between low-level UPR and proliferation, and reveal an UPR-independent anti-inflammatory islet cell response uncovered in the absence of IDE of potential interest in autoimmune diabetes.

cell biology↗

bioRxiv2022

Theileria annulata histone deacetylase 1 (TaHDAC1) initiates schizont to merozoite stage conversion

A fungal metabolite, FR235222, specifically inhibits a histone deacetylase of the apicomplexan parasite Toxoplasma gondii and TgHDAC3 has emerged as a key factor regulating developmental stage transition in this species. Here, we exploited FR235222 to ask if changes in histone acetylation regulate developmental stage transition of Theileria annulata, another apicomplexan species. We found that FR235222 treatment of T. annulata-infected transformed leukocytes induced a proliferation arrest. The blockade in proliferation was due to drug-induced conversion of intracellular schizonts to merozoites that lack the ability to maintain host leukocyte cell division. Induction of merogony by FR235222 leads to an increase in expression of merozoite-marker (rhoptry) proteins. RNA-seq of FR235222-treated T. annulata-infected B cells identified deregulated expression of 468 parasite genes including a number encoding parasite ApiAP2 transcription factors. Thus, similar to T. gondii, FR235222 inhibits T. annulata HDAC (TaHDAC1) activity and places parasite histone acetylation as a major regulatory event of the transition from schizonts to merozoites.

cell biology↗

bioRxiv2020

Single-nucleus RNA-seq and FISH reveal coordinated transcriptional activity in mammalian myofibers

Skeletal muscle fibers are large syncytia but it is currently unknown whether gene expression is coordinately regulated in their numerous nuclei. By snRNA-seq and snATAC-seq, we showed that slow, fast, myotendinous and neuromuscular junction myonuclei each have different transcriptional programs, associated with distinct chromatin states and combinations of transcription factors. In adult mice, identified myofiber types predominantly express either a slow or one of the three fast isoforms of Myosin heavy chain (MYH) proteins, while a small number of hybrid fibers can express more than one MYH. By snRNA-seq and FISH, we showed that the majority of myonuclei within a myofiber are synchronized, coordinately expressing only one fast Myh isoform with a preferential panel of muscle-specific genes. Importantly, this coordination of expression occurs early during post-natal development and depends on innervation. These findings highlight a unique mechanism of coordination of gene expression in a syncytium.

cell biology↗