Biology subjects

Yechoor, V. K.

Publications and source records attributed to Yechoor, V. K..

3 recordsLinked to original sources

bioRxiv2026

TEAD1 signaling modulates adrenal chromaffin maturation

Chromaffin cells synthesize and secrete catecholamines to coordinate systemic stress responses and regulate diverse neuroendocrine and metabolic functions. However, the molecular mechanisms governing chromaffin-cell differentiation and their disruption in pheochromocytoma (PC) remain incompletely understood. Here, through integrated analyses of human developmental atlases, patient-derived transcriptomic datasets, genetically engineered mouse models, and chromaffin organoids, we identify TEAD1 signaling as a critical regulator of chromaffin-cell differentiation and function. In vivo studies using a chromaffin cell-specific TEAD1 overexpression mouse model demonstrated that suppression of TEAD signaling markedly compromises chromaffin-cell differentiation and endocrine function. Additionally, compared with other TEAD family members, TEAD1 transcriptional activities are readily affected by sequences near the binding motif. To identify therapeutically actionable regulators of TEAD1 signaling, we established a TEAD activity-based screening platform and identified the serotonin receptor HTR5A antagonist SB699551 as a potent modulator of chromaffin-cell state. SB699551 suppressed PC-cell proliferation in vivo, and remodeled catecholamines synthesis in primary human PC cells. Additionally, application of SB699551 to human PC tumor revealed a subpopulation of primary chromaffin cells sensitive to this compound. Mechanistically, CXXC5 and L1CAM were identified as downstream SB699551-TEAD1 signaling effectors mediating chromaffin-cell proliferation and differentiation. Overall, we demonstrate that TEAD1 signaling is a fundamental mechanism regulating chromaffin cell differentiation and that modulation of TEAD1 signaling via SB699551 offers a new area of investigation in chromaffin cell biology.

molecular biology↗

bioRxiv2026

Single Cell Mapping Identifies CD14+ Macrophages as Central Orchestrators of CD8+ T Cell Driven Immune Niches in clinical Type 1 diabetes

The authors have withdrawn this manuscript after identifying an error in the annotation of donor disease status in one or more datasets used in the study. The error arose from inadequate or ambiguous disease-status labeling in the corresponding GEO dataset at NCBI. The authors personally communicated with the dataset depositor to verify the disease status of the relevant samples. Subsequent verification indicated that the deposited metadata required correction to accurately reflect the disease status of these samples, which may affect the results and interpretation of the study. The authors therefore took the initiative to work with the GEO/NCBI database administrators to correct the relevant sample annotations and are currently reassessing the analyses using the corrected metadata. The authors believe that withdrawal of the current version is appropriate until this reassessment is complete and a revised version can be prepared. This withdrawn version should not be cited or relied upon as a reference until a revised version is made available. Any questions regarding the withdrawal or ongoing reassessment should be directed to the corresponding author.

pathology↗

bioRxiv2025

Recapitulation of clinical and molecular hallmarks of lipid-induced hepatic insulin resistance in a zonated, vascularized human liver acinus microphysiological system during metabolic dysfunction-associated steatotic liver disease (MASLD) progression

Metabolic dysfunction-associated steatotic liver disease (MASLD) impacts ca. 30% of the global population and is very heterogeneous making it a challenge to produce therapeutics. The heterogeneity arises from genetics, co-morbidities, the microbiome and lifestyle. To help address this challenge, we have refined the human vascularized liver acinus microphysiological system (vLAMPS), which provides an all-human platform for drug development, in line with recently updated federal requirements for the use of New Approach Methodologies (NAMs). By introducing clinically relevant media perturbations and employing several diverse and reproducible in situ and systemic measurements, we show that the vLAMPS can recapitulate key structural and functional aspects of normal physiology, acinus zonation, and all stages of MASLD progression including stellate cell activation and fibrosis. Importantly, in this study we also demonstrate that several hallmarks of lipid-induced hepatic insulin resistance paralleled MASLD progression. These included diminution of insulin receptor substrate 2 (IRS2) protein, compromised insulin receptor mediated insulin clearance, enhanced pericentral lipid accumulation, increased VLDL secretion, and enhanced hepatic glucose output mediated by increased periportal nuclear translocation of FOXO1. These results suggest that the mechanisms underlying MASLD progression in vLAMPS are clinically relevant and support the tenable hypothesis that the hepatic insulin resistant state plays both a causal and consequential role in a vicious cycle driving disease progression.

bioengineering↗