Biology subjects

Bhuiyan, S.

Publications and source records attributed to Bhuiyan, S..

3 recordsLinked to original sources

bioRxiv2025

A transcriptomic comparison of the HD10.6 human sensory neuron-derived cell line with primary and iPSC sensory neurons

A key concern in early-stage analgesic discovery efforts is the extent to which mechanisms identified in rodents will translate to humans. To evaluate an alternative approach to the use of rodent dissociated DRG neurons for in vitro analyses of nociceptive signaling, we performed a transcriptomic analysis of the HD10.6 human dorsal root ganglion (DRG)-derived immortalized cell line. We conducted RNA-seq on proliferating and mature HD10.6 cells to characterize transcriptional changes associated with maturation. We then compared the transcriptomes of HD10.6 cells and several recently developed lines of human induced pluripotent stem cell-derived sensory neurons (iPSC-SN) to single-nucleus RNA-seq data from human DRGs. HD10.6 cells showed the highest correlation with 3 human sensory neuron subtypes associated with nociception and pruriception. Each of the iPSC-SN lines evaluated showed a distinct pattern of correlation with human sensory neuron subtypes. We identified G protein-coupled receptors (GPCRs) and ion channels that are expressed in both HD10.6 cells and human DRG neurons, as well as numerous genes that are expressed in human DRG but not in rodent, underscoring the need for human sensory neuron in vitro models. Proof-of-concept evaluations of protein kinase A, protein kinase C and Erk signaling provide examples of scalable assays using HD10.6 cells to investigate well-established GPCR signaling pathways. We conclude that HD10.6 cells provide a versatile model for exploring human neuronal signaling mechanisms.

neuroscience↗

bioRxiv2023

Harmonized cross-species cell atlases of trigeminal and dorsal root ganglia

Peripheral sensory neurons in the dorsal root ganglion (DRG) and trigeminal ganglion (TG) are specialized to detect and transduce diverse environmental stimuli including touch, temperature, and pain to the central nervous system. Recent advances in single-cell RNA-sequencing (scRNA-seq) have provided new insights into the diversity of sensory ganglia cell types in rodents, non-human primates, and humans, but it remains difficult to compare transcriptomically defined cell types across studies and species. Here, we built cross-species harmonized atlases of DRG and TG cell types that describe 18 neuronal and 11 non-neuronal cell types across 6 species and 19 studies. We then demonstrate the utility of this harmonized reference atlas by using it to annotate newly profiled DRG nuclei/cells from both human and the highly regenerative axolotl. We observe that the transcriptomic profiles of sensory neuron subtypes are broadly similar across vertebrates, but the expression of functionally important neuropeptides and channels can vary notably. The new resources and data presented here can guide future studies in comparative transcriptomics, simplify cell type nomenclature differences across studies, and help prioritize targets for future pain therapy development.

neuroscience↗

bioRxiv2018

Systematic evaluation of isoform function in literature reports of alternative splicing

Although most mammalian genes have multiple isoforms, an ongoing debate is whether these isoforms are all functional as well as the extent to which they increase the genomes functional repertoire. To ground this debate in data, we established a curation framework for evaluating experimental evidence of functionally distinct splice isoforms (FDSIs) and analyzed splice isoform function for over 700 human and mouse genes. Despite our bias towards prominently studied genes, we found experimental evidence meeting the classical definition for functionally distinct isoforms for only ~5% of the curated genes. If we relax our criteria, the fraction of genes with support for FDSIs remains low (~13%). We provide evidence that this picture will not change substantially with further curation. Furthermore, many FDSIs did not trace to a specific isoform in Ensembl. Our work has implications for computational analyses of alternative splicing and should help shape research around the role of splicing on gene function from presuming large general effects to acknowledging the need for stronger experimental evidence.

molecular biology↗