Biology subjects

Scott, J. K.

Publications and source records attributed to Scott, J. K..

4 recordsLinked to original sources

bioRxiv2025

Tyrosine kinase inhibitors affect sweet taste and dysregulate fate selection of specific taste cell subtypes via KIT inhibition.

Taste dysfunction, or dysgeusia, is a common side effect of many cancer drugs. Dysgeusia is often reported by patients treated with anti-angiogenic tyrosine kinase inhibitors (TKIs), which inhibit receptor tyrosine kinases (RTKs). However, the mechanisms by which TKIs cause dysgeusia are not understood, as the role of RTKs in adult taste homeostasis is unknown. Here, we find that treating adult mice with the TKI cabozantinib shifts the fate of differentiating functional taste cell subtypes within taste buds. Through behavioral assays, we find this cell fate shift leads to blunted responses to sweet in cabozantinib-treated mice. Finally, we show that inducible knockout of the RTK KIT, which is inhibited by cabozantinib, phenocopies taste cell fate shifts induced by TKI treatment. Our results establish KIT as a regulator of taste cell homeostasis and suggest that KIT inhibition may underlie TKI-induced dysgeusia in patients. SummaryKIT signaling blockade by tyrosine kinase inhibitors alters the fate of functional taste bud cell subtypes.

neuroscience↗

bioRxiv2024

A pipeline for facile cloning of antibody Fv domains and their expression, purification, and characterization as recombinant His-tagged IgGs

We report a functional pipeline for facile conversion of variable Fv domains, typically discovered in antibody discovery programs, into chimeric monoclonal antibodies (mAbs). Often, in initial screenings, a set of candidate mAbs is produced in small volumes and purified from supernatant for testing. Our pipeline also simplifies purification of mAbs by using an extended histidine tag (His-10) fused to the C-terminus of the light chain. Both the length of the His-10 and its location have been shown to affect the efficacy of mAb purification using an inexpensive nickel-based resin at neutral pH. Our antibody cloning and purification pipeline, when followed together with detection and affinity measurements, can be smoothly incorporated into an antibody discovery workflow.

immunology↗

bioRxiv2022

High Sox2 expression predicts taste lineage competency of lingual progenitors in vitro.

SO_SCPLOWUMMARYC_SCPLOWTaste buds on the tongue are collections of taste receptor cells (TRCs) that detect sweet, sour, salty, umami and bitter stimuli. Like non-taste lingual epithelium, TRCs are renewed from basal keratinocytes, many of which express the transcription factor SOX2. Genetic lineage tracing has shown SOX2+ lingual progenitors give rise to both taste and non-taste lingual epithelium in the posterior circumvallate taste papilla (CVP) of mice. However, SOX2 is variably expressed among CVP cells suggesting that their progenitor potential may vary. Using transcriptome analysis and organoid technology, we show highly expressing SOX2+ cells are taste-competent progenitors that give rise to organoids comprising both TRCs and lingual epithelium, while organoids derived from low-expressing SOX2+ progenitors are composed entirely of non-taste cells. Hedgehog and WNT/{beta}-catenin are required for taste homeostasis in adult mice, but only WNT/{beta}-catenin promotes TRC differentiation in vitro and does so only in organoids derived from higher SOX2+ taste lineage-competent progenitors.

developmental biology↗

bioRxiv2020

Onset of taste bud cell renewal starts at birth and coincides with a shift in SHH function.

Embryonic taste bud primordia are specified as taste placodes on the tongue surface and differentiate into the first taste receptor cells (TRCs) at birth. Throughout adult life, TRCs are continually regenerated from epithelial progenitors. Sonic hedgehog (SHH) signaling regulates TRC development and renewal, repressing taste fate embryonically, but promoting TRC differentiation in adults. Here we show TRC renewal initiates at birth and coincides with onset of SHHs pro-taste function. Using transcriptional profiling to explore molecular regulators of renewal, we identified Foxa1 and Foxa2 as potential SHH target genes in lingual progenitors at birth, and show SHH overexpression in vivo alters FOXA1 and FOXA2 expression relevant to taste buds. We further bioinformatically identify genes relevant to cell adhesion and cell locomotion likely regulated by FOXA1;FOXA2, and show expression of these candidates is also altered by forced SHH expression. We present a new model where SHH promotes TRC differentiation by regulating changes in epithelial cell adhesion and migration.

developmental biology↗