Biology subjects

Duteil, D.

Publications and source records attributed to Duteil, D..

4 recordsLinked to original sources

bioRxiv2026

Interdependent androgen and glucocorticoid receptor signalling shapes prostate epithelial homeostasis

Androgen signalling is essential for prostate secretory functions and epithelial cell maintenance, yet how this signal is translated into a transcriptional output remains poorly understood. Androgens functions are primarily mediated by the androgen receptor (AR), which binds hormone response elements similar to those of other steroid receptors, including the glucocorticoid receptor (GR). Here we show that AR and GR are co-expressed in the prostate epithelium, and co-located within nuclear foci. Moreover, GR promotes the formation and dynamics of AR nuclear condensates, and heterodimerizes with AR in a ligand-binding domain-dependent manner. In addition, subtle variations within the hormone response element sequence direct the co-recruitment of AR and GR into activator or repressor complexes to activate or repress gene expression. Finally, prostate-specific deletion of GR in mice disrupts AR nuclear distribution, impairs AR-dependent gene networks involved in epithelial maintenance, and promotes the expression of genes involved in metabolism and cell cycle, resulting in altered tissue homeostasis. Thus, these findings identify GR as an integral component of the AR transcriptional machinery in epithelial cells of the healthy prostate, and reveal how shared cis-regulatory elements are interpreted to generate distinct transcriptional outcomes.

cell biology↗

bioRxiv2025

Androgen receptor imprints satellite cells stemness and preserves their reservoir for lifelong regeneration and optimal repair

Skeletal muscle stem cells (MuSC) are the guardians of muscle regeneration, sustaining tissue integrity through a delicate balance of quiescence, activation, and lineage commitment. While numerous molecular cues have been implicated in regulating these processes, the influence of androgen receptor (AR) signaling, an essential hormonal pathway for male muscle physiology, has remained largely unexplored. Here, we show that AR expression defines quiescent MuSC and acts as a safeguard of their dormancy. Integrated multi-omic analyses reveal a redistribution of AR binding from quiescence-maintenance loci to regulatory elements driving activation and metabolic reprogramming during repair. Loss of AR in young adult mice disrupts this balance, precipitating premature cell-cycle entry, skewed division modalities, depletion of the stem cell reservoir, and destabilization of the niche. These defects converge with hallmarks of aging-associated androgen decline, while androgen supplementation restores regenerative competence. Together, our findings establish AR signaling as a pivotal determinant of MuSC fate and a cornerstone of skeletal muscle homeostasis.

developmental biology↗

bioRxiv2025

Glucocorticoid Receptor Signaling in Myeloid Cells Orchestrates Inflammation Resolution and Muscle Repair

Glucocorticoids are key regulators of inflammation and tissue repair, yet their precise role in muscle regeneration remains incompletely understood. Here, we investigate the impact of myeloid-specific glucocorticoid receptor (GR) invalidation on macrophage dynamics and muscle stem cell function following acute injury. We demonstrate that the loss of GR in myeloid cells leads to increased macrophage accumulation, driven by altered proliferation and recruitment, without affecting fibro-adipogenic progenitor differentiation or satellite cell proliferation and differentiation under steady-state conditions. Transcriptomic and cistrome analyses at early regeneration stages reveal that GR directly regulates gene networks involved in efferocytosis and cell cycle control in myeloid cells. Importantly, administration of dexamethasone during the pro-inflammatory phase markedly delays muscle regeneration by impairing monocyte-to-macrophage transition and promoting macrophage proliferation in a myeloid-GR dependent manner, ultimately reducing satellite cell proliferation and myogenesis. In contrast, dexamethasone treatment during the anti-inflammatory phase exerts limited effects on muscle recovery. Together, our findings uncover a critical temporal role of GR signaling in myeloid cells in coordinating inflammatory resolution and stem cell function during muscle repair, and highlight the complexity of glucocorticoid actions in regenerative contexts.

developmental biology↗

bioRxiv2025

Disrupted transcriptional networks regulated by CHD1L during neurodevelopment underlie the mirrored neuroanatomical and growth phenotypes of the 1q21.1 copy number variant

Distal 1q21.1 deletions and duplications are associated with variable phenotypes including autism, head circumference and height defects. To elucidate which gene(s) are responsible for the 1q21.1 duplication/deletion-associated phenotypes, we performed gene manipulation in zebrafish and mice. We modeled 1q21.1 duplication by overexpressing the eight human protein-coding genes in zebrafish. We found that overexpression of CHD1L only led to macrocephaly and increased larval body length, whereas chd1l deletion caused opposite phenotypes. These mirrored phenotypes were also observed in mouse embryos. Transcriptomic, cistromic, and chromatin accessibility analyses of CHD1L knock-out hiPSC-derived neuronal progenitor cells revealed that CHD1L regulates the expression levels and chromatin accessibility of genes involved in neuronal differentiation and synaptogenesis, including autism genes. Moreover, we found that CHD1L favors telencephalon development during forebrain regionalization by facilitating chromatin accessibility to pioneer transcription factors including SOX2 and OTX2 while simultaneously compacting chromatin through its interaction with the repressor NuRD complex. Last, atypical 1q21.1 CNV encompassing CHD1L and pathogenic missense and truncating CHD1L variants were found in individuals with autism. Overall, our data reveal a novel role for CHD1L as a master regulator of cell fate and its dosage imbalance contributes to the neuroanatomical and growth phenotypes associated with the 1q21.1 distal CNV. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=71 SRC="FIGDIR/small/638841v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@7dd5borg.highwire.dtl.DTLVardef@55a12dorg.highwire.dtl.DTLVardef@1c8ce0corg.highwire.dtl.DTLVardef@4faf29_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗