Biology subjects

Beaudin, A.

Publications and source records attributed to Beaudin, A..

3 recordsLinked to original sources

bioRxiv2024

ARHGEF3 Regulates Hair Follicle Morphogenesis

During embryogenesis, cells arrange into precise patterns that enable tissues and organs to develop specialized functions. Despite its critical importance, the molecular choreography behind these collective cellular behaviors remains elusive, posing a major challenge in developmental biology and limiting advances in regenerative medicine. By using the mouse hair follicle as a mini-organ system to study the formation of bud-like structures during embryonic development, our work uncovers a crucial role for the Rho GTPase regulator ARHGEF3 in hair follicle morphogenesis. We demonstrate that Arhgef3 expression is upregulated at the onset of hair follicle placode formation. In Arhgef3 knockout animals, we observed defects in placode compaction, leading to impaired hair follicle downgrowth. Through cell culture models, we show that ARHGEF3 promotes F-actin accumulation at the cell cortex and P-cadherin enrichment at cell-cell junctions. Collectively, our study identifies ARHGEF3 as a new regulator of cell shape rearrangements during hair placode morphogenesis, warranting further exploration of its role in other epithelial appendages that arise from similar developmental processes.

developmental biology↗

bioRxiv2024

An age-specific platelet differentiation path from hematopoietic stem cells contributes to exacerbated thrombosis

Platelet dysregulation is drastically increased with advanced age and contributes to making cardiovascular disorders the leading cause of death of elderly humans. Hematopoietic stem and progenitor cells continuously give rise to platelets, but their contributions to variable platelet production and activity throughout life remain unclear. Here we reveal a direct differentiation pathway from hematopoietic stem cells into platelets that is unique to aging. An unequivocal genetic lineage tracing mouse model demonstrated that this age-specific pathway is progressively propagated over time. Remarkably, the age-specific platelet path is decoupled from all other hematopoietic lineages, including erythropoiesis, and operates as an additional layer in parallel with canonical platelet production. This results in two molecularly and functionally distinct populations of megakaryocyte progenitor cells that that operate in parallel. The age-specific megakaryocyte progenitor population has profoundly enhanced capacity to engraft, expand, and reconstitute platelets, and produces an additional platelet population that exists only in old mice. Consistent with increased thrombotic incidence upon aging, the two pools of co-existing platelets contribute to age-related thrombocytosis and dramatically increased thrombosis in vivo. Upon acute, platelet-specific stress, the age-specific MkPs endowed old mice with superior capacity to rapidly restore platelet counts. These findings reveal stem cell-based aging as a mechanism for platelet dysregulation and identify an aging-induced population of functionally enhanced MkPs as a unique source of age-specific platelets. >HIGHLIGHTSO_LIAging leads to two parallel platelet specification paths from HSCs C_LIO_LIThe shortcut platelet pathway is perpetuated by highly expansive MkPs unique to aging C_LIO_LIThe age-specific differentiation path contributes to thrombosis and platelet hyperreactivity C_LIO_LIAge-specific MkPs serve as potent first responders to acute platelet loss C_LI

cell biology↗

bioRxiv2019

The lymphoid-associated interleukin 7 receptor (IL-7R) regulates tissue resident macrophage development

The discovery of a fetal origin for tissue-resident macrophages (trMacs) has inspired an intense search for the mechanisms underlying their development. Here, we performed in vivo lineage tracing of cells with an expression history of IL-7R, a marker exclusively associated with the lymphoid lineage in adult hematopoiesis. Surprisingly, we found that IL7R-Cre labeled fetal-derived, adult trMacs. Labeling was almost complete in some tissues and partial in other organs. The putative progenitors of trMacs, yolk sac (YS) erythromyeloid progenitors (EMPs), did not express IL-7R, and YS hematopoiesis was unperturbed in IL-7R-deficient mice. In contrast, tracking of IL-7R message levels, surface protein expression, and IL7R-Cre-mediated labeling across fetal development revealed dynamic regulation of IL-7R mRNA expression and rapid upregulation of IL-7R surface protein upon transition from monocyte to macrophage within fetal tissues. Fetal liver monocyte differentiation in vitro produced IL-7R+ macrophages, supporting a direct progenitor-progeny relationship. Additionally, blockade of IL-7R function during late gestation specifically impaired the establishment of fetal-derived tissue macrophages in vivo. These data provide evidence for a distinct function of IL-7R in fetal myelopoiesis and identify IL-7R as a novel regulator of tissue-resident macrophage development.

immunology↗