Biology subjects

Bard, J. E.

Publications and source records attributed to Bard, J. E..

4 recordsLinked to original sources

bioRxiv2026

Myosin-9b Controls Epithelial Brush Border Architecture through Motility-Dependent RhoA Signaling

Genetic variations in the MYO9B gene have been associated with Crohn's disease, celiac disease, and ulcerative colitis. These diseases have been characterized as primarily immune disorders. However, the overall molecular basis for the influence of Myo9b in these diseases remains poorly understood. Using in vivo small intestine ileum and human cell culture models, we identify a molecular function for Myo9b in the regulation of epithelial brush border microvilli. Using live-cell super-resolution microscopy, we characterize the motility of Myo9b as it moves toward enriched puncta at the tips of microvilli and visualize its direct regulation of small GTPase signaling using an active RhoA biosensor. In Myo9b knockout cells, microvilli abundance and dynamics are altered, but the cells ultimately maintain the presence of microvilli and the appropriate incorporation of microvilli specific cytoskeletal to membrane regulators such as Ezrin. Alternatively, expression of the Myo9b-S1011A disease variant as the only genetic copy in human cells results in a total loss of microvilli and Ezrin apical localization. These results indicate that Myo9b is a critical regulator of epithelial cell morphology and microvilli. Further, our data establish that the S1011A disease variant disrupts microvilli in human cells, suggesting a potential mechanistic link to its involvement in disease states.

cell biology↗

bioRxiv2026

Cell-type-specific ATF6α programs regulate epithelial mitochondrial homeostasis and pericyte remodeling during physiological and exposure-accelerated lung aging

Proteostasis declines with lung aging, while the role of the Unfolded Protein Response (UPR) in lung aging and age-associated pulmonary diseases remains understudied. We investigated how deficiency in the UPR sensor ATF6 affects physiological and smoke exposure-accelerated lung aging. ATF6 -deficient mice exhibited accelerated alveolar simplification, a sign of lung parenchymal aging, which was exacerbated by smoking. Nevertheless, small airway vascular fibrotic remodeling, a prominent smoking-induced pathology, was not evident in smoke-exposed ATF6 -deficient mice. Mechanistically, these divergent phenotypes arose from cell-type-specific ATF6 programs. In alveolar epithelial type 2 cells (AEC2s), the facultative progenitors of the lung parenchyma, ATF6 maintained mitochondrial bioenergetics and sustained efficient redifferentiation into alveolar epithelial type 1 cells (AEC1s). In lung pericytes, ATF6 promoted extravasation, redifferentiation into myofibroblast-like cells, and production of collagens 1 and 3. These findings identify ATF6 as a cell-type-specific regulator of differentiation programs during lung aging and highlight the need to study ATF6 under defined physiological and pathological contexts before therapeutically targeting this pathway.

cell biology↗

bioRxiv2026

Chemotherapy-Induced Oral Mucosal Injury Is Defined by p53 Activation, Cell Cycle Arrest and Diverse Epithelial Progenitor Dynamics

Chemotherapy-induced oral mucositis is a common and debilitating complication, yet the mechanisms underlying oral mucosa injury and repair remain poorly defined. Using a mouse model of 5-fluorouracil (5-FU)-induced mucositis, we define gene networks and oral mucosal cellular landscape dynamics in response to chemotoxic stress. We show that 5-FU-induced epithelial atrophy is driven primarily by cell cycle arrest rather than apoptosis, despite concurrent activation of p53-dependent transcriptional programs linked to both cell fates within individual cells. Relative to intestine, the recovering oral mucosa exhibits a more effective cell cycle checkpoint response and uniquely undergoes metabolic reprogramming toward lipid oxidation. Single-cell RNA sequencing revealed putative epithelial progenitor populations with distinct responses to chemotherapy, including chemoresistant cells with a p53- and AP-1 complex gene signature, reminiscent of lung transitional cell states. These findings define diverse progenitor dynamics and p53-driven responses as key determinants of oral mucosal injury and repair following chemotherapy.

cell biology↗

bioRxiv2020

RNA-seq and scRNA-seq reveal trajectory progression of the retinal ganglion cell lineage in wild-type and Atoh7-null retinas

Past studies concluded that Atoh7 is critical for the emergence of the retinal ganglion cell (RGC) lineage in the developing retina, whereas Pou4f2 and Isl1 function in RGC differentiation. Atoh7 is expressed in a subset of retinal progenitor cells (RPCs) and is considered a competence factor for the RGC fate, but the molecular properties of these RPCs have not been well characterized. In this study, we first used conventional RNA-seq to investigate transcriptomic changes in Atoh7-, Pou4f2-, and Isl1-null retinas at embryonic (E) day 14.5 and identified the differentially expressed genes (DEGs), which expanded our understanding of the scope of downstream events. We then performed single cell RNA-seq (scRNA-seq) on E13.5 and E17.5 wild-type and Atoh7-null retinal cells. Clustering analysis not only correctly identified known cell types at these developmental stages but also revealed a transitional cell state which was marked by Atoh7 and genes for other lineages in a highly overlapping fashion and shared by all early developmental trajectories. Further, analysis of the Atoh7-null retina revealed that, unlike previously believed, the RGC lineage still progressed considerably and a substantial amount of RGC-specific gene expression still occurred. Thus, Atoh7 likely collaborates with other factors to shepherd the transitional RPCs to the RGC lineage by competing with other lineage factors and activating RGC-specific genes. This study thus provides significant insights into the nature of RPC competence for different retinal cell fates and revises our current view on the emergence of the RGC lineage.

developmental biology↗