Biology subjects

Jarvis, B.

Publications and source records attributed to Jarvis, B..

5 recordsLinked to original sources

bioRxiv2026

Spatial analysis of Intraductal Papillary Mucinous Neoplasms reveals secretory cell-enriched neighborhoods

Pancreatic ductal adenocarcinoma (PDAC) is currently the third leading cause of cancer-related deaths in the United States. Intraductal papillary mucinous neoplasms (IPMNs) are neoplastic lesions of ductal origin that seed 10-25% of PDAC. There are currently no markers that distinguish between IPMN that will remain benign and those that will progress to cancer. A heterogenous population of secretory cells, including chemosensory tuft cells and hormone-expressing enteroendocrine cells (EECs), form during metaplasia and neoplastic progression in the pancreas, but the relevance of these populations as it relates to IPMN progression is not well characterized. Here, we performed spatial transcriptomics as well as multiplex immunostaining and spatial statistics on surgically resected IPMN from 60 patients to characterize these populations in all subtypes (gastric foveolar, intestinal, pancreatobiliary) and grades (low-grade, high-grade, invasive). We found that POU2F3+ tuft-like cells, CHGA+ EECs, and a subset of pancreatic endocrine cells ([a] and {gamma} cells) were present in all types of IPMN. Further, serotonin-expressing enterochromaffin cells made up the bulk of EECs in low-grade disease. Enterochromaffin, tuft-like, and glucagon-expressing alpha cells were not evenly distributed and instead were significantly enriched in a spatial manner, which is overlooked using conventional whole tissue quantification approaches. Tuft-like cell clusters were enriched with monocytes and resident memory T cells and anti-correlated to activated fibroblasts (myCAFs, iCAFs). Overall, these secretory cell clusters may reflect clonal expansion resulting in formation of distinct stromal niches with unknown consequences for disease progression.

Cancer Biology↗

bioRxiv2026

Motor Intention Drives Corticospinal Facilitation during Interception Planning

Intercepting a moving target requires integrating visual motion information with motor preparation, yet how active motor preparation and gaze strategy jointly shape corticospinal excitability during interception planning remains unclear. We applied single-pulse transcranial magnetic stimulation over primary motor cortex to probe corticospinal excitability while participants either prepared to intercept a moving target or passively viewed its motion. Targets moved at one of two speeds, and participants judged target speed relative to a reference after each trial. Across blocks, participants were instructed to either smoothly pursue the target or fixate their eyes on the interception zone. Motor-evoked potentials were elicited at baseline, after task instruction, early during target motion, or shortly before target arrival. Task and gaze strategy interacted to influence both perceptual judgments and corticospinal excitability. Preparing to intercept produced a robust facilitation of corticospinal excitability immediately before movement onset, regardless of gaze strategy. In contrast, corticospinal excitability during passive viewing did not differ from baseline. Smooth pursuit improved perceptual accuracy and reduced interception timing error compared with fixation but did not independently influence corticospinal facilitation. These findings demonstrate that active motor preparation is the primary determinant of the transition to a state of facilitated excitability during interception planning, whereas eye movements modulate perceptual estimates and support behavioral performance. New & NoteworthyThis study dissociates the contributions of visual tracking, eye movements, and active motor preparation to corticospinal excitability during interception. Here, we show that corticospinal facilitation emerges primarily when an action is planned, whereas passive viewing remains at baseline despite identical visual input. Smooth pursuit enhanced perceptual accuracy and interception timing but had a limited effect on corticospinal excitability, highlighting active motor preparation as the key driver of corticospinal output.

neuroscience↗

bioRxiv2025

Pcdh20 is a POU2F3 target gene required for proper tuft cell microvillus formation

BACKGROUND & AIMSTuft cells play protective roles in infection, inflammation, and tumorigenesis through the secretion of cytokines and eicosanoids. Tuft cells are known for their tall, blunt microvilli, thought to be analogous to mechanosensory hair cell stereocilia; however, a functional role for the microvillar apparatus has not been identified. POU2F3 is the master regulator transcription factor for tuft cells, yet how POU2F3 drives formation of this unique structure is unknown. Here, we aimed to identify POU2F3 target genes and commonalities between tuft and hair cells to better understand this unique structure. METHODSPOU2F3 ChIP-seq was performed on tuft cells and compared to the hair cell transcriptome. Tuft cell RNA-seq datasets were interrogated for hair cell structural and mechanosensory genes; expression was validated. Intestinal and gallbladder tuft cells were examined using multiple light and electron microscopy (EM) modalities. PCDH20 was knocked down in mouse models and ultrastructural analyses were performed. The tuft cell cytoskeleton was modeled using AlphaFold3 prediction. RESULTSGenes encoding structural and mechanosensory proteins common to both tuft and hair cells, including Pcdh20, were identified. Imaging localized PCDH20 to tuft cell microvilli and hair cell stereocilia. Genetic ablation of Pcdh20 in mice resulted in structural defects in tuft cell microvilli, including loss of rigidity and organization. Molecular modeling suggests PCDH20 homodimers link adjacent microvilli. CONCLUSIONSPcdh20 is a POU2F3 target gene in tuft cells, critical to maintain the rigid microvillar apparatus. These findings, together with the shared expression of mechanosensory components like TMC1, support the hypothesis that tuft cells could have mechanosensory capabilities analogous to cochlear hair cells.

cell biology↗

bioRxiv2024

Oncogenic GNAS drives a gastric pylorus program in intraductal papillary mucinous neoplasms of the pancreas

BACKGROUND & AIMSIntraductal Papillary Mucinous Neoplasms (IPMNs) are cystic lesions and bona fide precursors for pancreatic ductal adenocarcinoma (PDAC). Recent studies have shown that pancreatic precancer is characterized by a transcriptomic program similar to gastric metaplasia. The aims of this study were to assay IPMN for pyloric markers, to identify molecular drivers, and to determine a functional role for this program in the pancreas. METHODSPyloric marker expression was evaluated by RNA-seq and multiplex immunostaining in patient samples. Cell lines and organoids expressing KrasG12D +/- GNASR201C underwent RNA sequencing. A PyScenic-based regulon analysis was performed to identify molecular drivers, and candidates were evaluated by RNA-seq, immunostaining, and small interfering RNA knockdown. Glycosylation profiling was performed to identify GNASR201C-driven changes. Glycan abundance was evaluated in patient samples. RESULTSPyloric markers were identified in human IPMN. GNASR201Cdrove expression of this program as well as an indolent phenotype characterized by distinct glycosyltransferase changes. Glycan profiling identified an increase in LacdiNAcs and loss of pro-tumorigenic Lewis antigens. Knockdown of transcription factors Spdef or Creb3l1 or chitinase treatment reduced LacdiNAc deposition and reversed the indolent phenotype. LacdiNAc and 3-sulfoLeA/C abundance discriminated low from high grade patient IPMN. CONCLUSIONGNASR201C drives an indolent phenotype in IPMN by amplifying a differentiated, pyloric phenotype through SPDEF/CREB3L1 which is characterized by distinct glycans. Acting as a glycan rheostat, mutant GNAS elevates LacdiNAcs at the expense of pro-tumorigenic acidic Lewis epitopes, inhibiting cancer cell invasion and disease progression. LacdiNAc and 3-Sulfo-LeA/C are mutually exclusive and may serve as markers of disease progression.

cancer biology↗

bioRxiv2021

Chromosome-level Thlaspi arvense genome provides new tools for translational research and for a newly domesticated cash cover crop of the cooler climates

Thlaspi arvense (field pennycress) is being domesticated as a winter annual oilseed crop capable of improving ecosystems and intensifying agricultural productivity without increasing land use. It is a selfing diploid with a short life cycle and is amenable to genetic manipulations, making it an accessible field-based model species for genetics and epigenetics. The availability of a high quality reference genome is vital for understanding pennycress physiology and for clarifying its evolutionary history within the Brassicaceae. Here, we present a chromosome-level genome assembly of var. MN106-Ref with improved gene annotation, and use it to investigate gene structure differences between two accessions (MN108 and Spring32-10) that are highly amenable to genetic transformation. We describe small RNAs, pseudogenes, and transposable elements, and highlight tissue specific expression and methylation patterns. Resequencing of forty wild accessions provides insights into genome-wide genetic variation as well as QTL regions for flowering time and a seedling color phenotype. Altogether, these data will serve as a tool for pennycress improvement in general and for translational research across the Brassicaceae.

plant biology↗