Biology subjects

Tsai, N.

Publications and source records attributed to Tsai, N..

3 recordsLinked to original sources

bioRxiv2026

The Logic of Thalamic Inputs onto the Molecular Taxonomy of Cortical Neurons Reveals a Visual Hierarchy

The hierarchical organization of sensory cortices and the rich molecular taxonomy of their cell types are defining features of the mammalian cortex. Cortical areas along this hierarchy are reciprocally connected via the thalamus through bottom-up and top-down projections. The logic through which these projections map onto the cellular taxonomy of the cortex is, however, poorly understood. Here we combine an anterograde transsynaptic tracer with spatial transcriptomics to reveal the molecular and spatial identity of mouse visual cortical neurons downstream of thalamic starter neurons across visual cortical areas. Distinct thalamic inputs target characteristic sets of molecularly defined cortical neurons, forming bottom-up or top-down "signatures" defined by cell-type composition and the ratio of GABAergic to glutamatergic neurons. These signatures reveal a hierarchy spanning thalamic nuclei and visual cortical areas, independently predicted by the molecular and cellular similarities between cortical areas. This work uncovers basic principles of how bottom-up and top-down thalamic inputs map onto the cellular taxonomy in the visual cortex and establishes a cellular framework for the cortical hierarchy.

neuroscience↗

bioRxiv2019

Single-cell analysis of human retina identifies evolutionarily conserved and species-specific mechanisms controlling development.

The development of single-cell RNA-Sequencing (scRNA-Seq) has allowed high resolution analysis of cell type diversity and transcriptional networks controlling cell fate specification. To identify the transcriptional networks governing human retinal development, we performed scRNA-Seq over retinal organoid and in vivo retinal development, across 20 timepoints. Using both pseudotemporal and cross-species analyses, we examined the conservation of gene expression across retinal progenitor maturation and specification of all seven major retinal cell types. Furthermore, we examined gene expression differences between developing macula and periphery and between two distinct populations of horizontal cells. We also identify both shared and species-specific patterns of gene expression during human and mouse retinal development. Finally, we identify an unexpected role for ATOH7 expression in regulation of photoreceptor specification during late retinogenesis. These results provide a roadmap to future studies of human retinal development, and may help guide the design of cell-based therapies for treating retinal dystrophies.

neuroscience↗

bioRxiv2018

Single-cell RNA-seq analysis maps the development of human fetal retina

Vision starts with image formation at the retina, which contains diverse neuronal cell types that extract, process, and relay visual information to higher order processing centers in the brain. Though there has been steady progress in defining retinal cell types, very little is known about retinal development in humans, which starts well before birth. In this study, we performed transcriptomic profiling of developing human fetal retina from gestational weeks 12 to 27 using single-cell RNA-seq (scRNA-seq) and used pseudotime analysis to reconstruct the developmental trajectories of retinogenesis. Our analysis reveals transcriptional programs driving differentiation down four different cell types and suggests that Muller glia (MG) can serve as embryonic progenitors in early retinal development. In addition, we also show that transcriptional differences separate retinal progenitor cells (RPCs) into distinct subtypes and use this information to reconstruct RPC developmental trajectories and cell fate. Our results support a hierarchical program of differentiation governing cell-type diversity in the developing human retina. In summary, our work details comprehensive molecular classification of retinal cells, reconstructs their relationships, and paves the way for future mechanistic studies on the impact of gene regulation upon human retinogenesis.

neuroscience↗