Biology subjects

Boyer, T.

Publications and source records attributed to Boyer, T..

6 recordsLinked to original sources

bioRxiv2026

Genome-resolved ecology and evolution of the microbiome enabled by quantitative long-read metagenomics

Standard metagenomics resolves microbial communities only in relative terms and at coarse taxonomic resolution, obscuring how individual strains change in absolute abundance and evolve within a host. We present long-read quantiomics (LRQ), a quantitative metagenomics platform coupling long-read sequencing with plasmid-based internal standards to recover high-quality genomes, including from degraded or low-input stool, and measure absolute, genome-resolved strain abundances. We validate LRQ using large plasmid standards and bacterial spike-ins, then apply it to eight years of dense sampling from an individual with colonic Crohn's disease. LRQ resolves co-resident strains of the same species following opposing trajectories with inflammation. Escherichia coli, long treated as a single pathobiont, separates into two sub-populations with opposing inflammation responses; the inflammation-associated lineage carries an immune-evasion module of virulence-associated metal-acquisition, biofilm, capsule and toxin genes. We observe genome-wide adaptive sweeps on timescales matched to disease incidence. LRQ therefore converts long-read metagenomics from a genome-recovery tool into a quantitative framework providing absolute, strain-level measurement of microbial ecology and evolution.

microbiology↗

bioRxiv2026

Static2Dynamic: Reconstructing videos of unobservable cellular, developmental, and disease processes

A fundamental limitation in biology is that many of its most important processes unfold as visual dynamics that cannot be directly observed. Development, tissue remodeling, and disease progression often occur deep in living organisms, over extended timescales, and at cellular resolution beyond the reach of current live imaging technologies. As a result, much of biology remains accessible only through static snapshots, while the underlying phenotypic trajectories and visual transformations remain hidden. Here, we introduce Static2Dynamic, a general framework to reconstruct unseen biological dynamics from sets of cross-sectional image data. Starting from time-unpaired static samples, Static2Dynamic first recovers a continuous pseudotime for individual images in a time-discriminative deep representation space, then learns a generative model of images conditionally to the underlying process, and finally reconstructs temporally coherent videos initialized from real samples. This makes it possible to infer past and future visual states of a static image and to simulate complete trajectories of cellular, developmental, and disease processes that were never directly recorded. We quantitatively validate Static2Dynamic on two large-scale experimental microscopy video datasets generated specifically for benchmarking, enabling direct comparison of inferred pseudotime trajectories and reconstructed videos against ground-truth biological dynamics. We further show that the framework generalizes across biological scales, organisms, and imaging modalities, including processes inaccessible to continuous live observation. More broadly, Static2Dynamic establishes the foundations of pseudotime microscopy, a new paradigm for reconstructing the visual and temporal dynamics of biological processes directly from static imaging data, thereby expanding the observable space of living systems beyond current experimental limits.

bioinformatics↗

bioRxiv2025

Vitamin D3 ameliorates R-loop-induced replication stress and chromosomal instability in MED12-mutant uterine fibroids

Uterine fibroids (UFs) are the most important benign neoplastic threat to womens health worldwide, with no long-term noninvasive treatment options currently available. Among known UF driver alterations, somatic mutations in Mediator subunit MED12 are by the far the most prevalent, accounting for up to 80% of these clinically significant lesions. Although it is presently unclear how MED12 mutations trigger neoplastic transformation, MED12-mutant UFs are nonetheless characterized by significant chromosomal loss and rearrangement, suggesting genomic instability as a driving force in tumor development. However, the basis by which MED12 mutations drive genomic instability is not known. Herein, we show that R-loop-driven replication stress in MED12-mutant UFs leads to DNA under-replication and mitotic segregation errors that drive chromosomal instability. Notably, we find that vitamin D3 (VD3), a modifiable risk factor in UF development, suppresses pathogenic R-loop accrual and ameliorates replication stress-driven chromosomal instability, contributing to growth inhibition of patient-derived MED12-mutant UF xenografts in vivo. Altogether these findings uncover a molecular basis by which the predominant UF driver converges with a known risk factor at the interface of genomic instability, with significant translational implications for personalized UF prevention and treatment.

molecular biology↗

bioRxiv2025

Immunosuppressive myeloid cells induce mesenchymal-like breast cancer stem cells by a mechanism involving membrane-bound TGF-β1.

Suppressive myeloid cells play a central role in cancer escape from anti-tumor immunity. Beyond their immunosuppressive function, these cells are capable of exerting multiple other pro-tumoral activities, including the promotion of cancer cell survival, invasion and metastasis. The ability of some myeloid subsets to induce cancer stemness has recently emerged. Here we demonstrated that human immunosuppressive myeloid cells, generated in vitro or isolated from breast cancer patients, promoted the acquisition of mesenchymal-like breast cancer stemness properties. This cancer-stemness-inducing function was restricted to a myeloid subset expressing the glycoprotein CD52. Single cell transcriptomic- and surface proteome-based interactome analysis pointed towards membrane-bound TGF-{beta}1 as a potential factor involved in cancer stemness induction. Functional inhibition of the TGF-{beta}1 pathway blocked the emergence of cancer stem cells induced by suppressive myeloid cells. These results therefore identified the underlying mechanisms of a new tumor-promoting function of immunosuppressive myeloid cells, which may potentially be targeted. HighlightsO_LIImmunosuppressive CD33highCD52+ myeloid cells induce mesenchymal-like cancer stem cells C_LIO_LICancer stemness induction requires membrane bound TGF-{beta}1 C_LIO_LIBlockade of the TGF-{beta}1 pathway prevents cancer stemness induction C_LI

cancer biology↗

bioRxiv2023

Tetraspanin CD81 promotes leukemia stem cell function and represents a new therapeutic vulnerability in acute myeloid leukemia

Despite important progress over the last decade, acute myeloid leukemia (AML) is still associated with poor clinical outcome. Novel potent therapies ideally effective against AML stem cells (LSC), a major driver of leukemia initiation and progression, are urgently needed. In particular, targeting common AML-associated antigens at the stem and progenitor cell level represents an attractive therapeutic strategy to achieve deep long-term remissions and is currently the subject of intensive research efforts. In this study, we identified the tetraspanin CD81, a cell surface antigen frequently expressed on AML cells including LSC, as a new determinant of relapse and poor prognosis. CD81 expression was higher in AML cells compared to normal bone marrow cells, and more markedly expressed at relapse. We further showed that modulation of CD81 expression using gain- and loss-of-function approaches affected leukemia aggressiveness, tumor burden, LSC-homing and - xenoengraftment as well as mouse survival. Finally, anti-hCD81 monoclonal antibody-treatment combined with standard chemotherapy in mice with pre-established AML not only reduced leukemia burden but also prolonged relapse-free and overall survival. Collectively, these results identified a new efficacious and safe pharmacological strategy for targeting LSC, opening up novel therapeutic avenues to improve AML outcome. Key pointsO_LICD81 expression in AML including LSC is a new determinant of aggressive disease and poor prognosis. C_LIO_LIAnti-hCD81 monoclonal antibody-treatment of AML xenografts reduced leukemia burden and improved survival rates. C_LI

cancer biology↗

bioRxiv2022

TREM1+ regulatory myeloid cells expand in steatohepatitis-HCC and associate with poor prognosis and therapeutic resistance to anti-PD-1 blockade

Hepatocellular carcinoma (HCC) is an inflammation-associated cancer arising from viral and non-viral etiologies. Immune checkpoint blockade primarily benefits patients with viral HCC. Expansion of suppressive myeloid cells is a hallmark of chronic inflammation and cancer, but their heterogeneity in HCC is not fully resolved and might underlie immunotherapy resistance in the steatohepatitis setting. Here, we present a high resolution atlas of hepatic innate immune cells from patients with HCC that unravels a steatohepatitis contexture characterized by the emergence of high entropy myeloid cell states and myeloid-biased NK cell differentiation. We identify a discrete population of tumor-infiltrating myeloid cells, predominant in the steatohepatitis setting, that expresses a variety of myeloid lineage-affiliated genes, including granulocyte, macrophage and dendritic cell features, and can be identified in HCC tumors based on selective dual expression of TREM1 and CD163. Functional characterization reveals that TREM1+ CD163+ myeloid cells highly express TGF{beta} and IL-13RA, localize to HCC fibrotic lesions, and potently suppress T cell effector functions ex vivo, a function further potentiated by TREM1 engagement. We refer to this population as TREM1+ CD163+ regulatory myeloid cells (TREM1+CD163+ Mreg). Deconvolution analyses in large cohorts of patients with HCC and other solid tumors reveals that the density of TREM1+ CD163+ Mreg increases in advanced stages, associates with poor prognosis, and therapeutic resistance to PD-1 blockade. Our data support myeloid subset-targeted immunotherapies to treat HCC and identify TREM1 as a therapeutic target. HIGHLIGHTSO_LIAtlas of hepatic innate immune cells (100,000 transcriptomes) from patients with HCC C_LIO_LICore signatures to identify, discriminate and localize innate lymphoid and myeloid cells C_LIO_LIA population of TREM1+CD163+ myeloid cells, referred to as TREM1+CD163+ Mreg, expands in steatohepatitis HCC C_LIO_LITREM1+CD163+ Mreg express granulocyte- and macrophage/dendritic cell-lineage genes C_LIO_LITREM1+CD163+ Mreg potently suppress T cell effector functions, which is potentiated by TREM1 engagement by cognate ligands C_LIO_LITREM1+CD163+ Mreg produce high levels of TGF{beta} and populate fibrotic lesions C_LIO_LIThe density of TREM1+CD163+ Mreg increases in advanced HCC and associate with poor patient survival C_LIO_LIThe density of TREM1+CD163+ Mreg associates with resistance to immune checkpoint blockade in other solid tumors C_LI

immunology↗