Publications

The cochlea uses two types of mechanosensory cell to detect sounds. A single row of inner hair cells (IHCs) synapse onto neurons to transmit sensory information to the brain, and three rows of outer hair cells (OHCs) selectively amplify auditory inputs1. So far, two transcription factors have been implicated in the specific differentiation of OHCs, whereas, to our knowledge, none has been identified in the differentiation of IHCs2-4.

Animals constantly receive various sensory stimuli, such as odours, sounds, light and touch, from the surrounding environment. These sensory inputs are essential for animals to search for food and avoid predators, but they also affect their physiological status, and may cause diseases such as cancer. Malignant gliomas-the most lethal form of brain tumour1-are known to intimately communicate with neurons at the cellular level2,3. However, it remains unclear whether external sensory stimuli can directly affect the development of malignant glioma under normal living conditions.

Cellular diversification is critical for specialized functions of the brain including learning and memory1. Single-cell RNA sequencing facilitates transcriptomic profiling of distinct major types of neuron2-4, but the divergence of transcriptomic profiles within a neuronal population and their link to function remain poorly understood. Here we isolate nuclei tagged5 in specific cell types followed by single-nucleus RNA sequencing to profile Purkinje neurons and map their responses to motor activity and learning.

Tuft cells are a rare chemosensory lineage that coordinates immune and neural responses to foreign pathogens in mucosal tissues1. Recent studies have also revealed tuft cell-like human tumors2,3, particularly as a variant form of small cell lung cancer (SCLC). Both normal and neoplastic tuft cells share a genetic requirement for the transcription factor POU2F32,4, although the transcriptional mechanisms that generate this cell type are poorly understood.

Astrocytes respond to injury and disease in the central nervous system with reactive changes that influence the outcome of the disorder1-4. These changes include differentially expressed genes (DEGs) whose contextual diversity and regulation are poorly understood.

Purpose : ADOA is the most common inherited optic neuropathy, starting in the first decade of life and resulting in severe and progressive visual decline due to loss of RGCs. Most patients harbor loss-of-function mutations in the OPA1 gene that lead to haploinsufficiency. Reduced OPA1 protein levels result in impaired mitochondrial function in RGCs leading to cell death. Currently, there is no treatment for patients with ADOA.

RESULTS : In rodent eye (both rat and mouse), CFH mRNA is strongly expressed in the retinal pigment epithelium with some expression also found in inner nuclear (INL) and retinal ganglion cell (RGC) layers of the retina. C3 mRNA is expressed mainly in RGC, INL of retina, ciliary body, corneal epithelium with some expression is also found in rodent retinal pigment epithelium layer. However, in human eye, CFH and C3 mRNA are strongly expressed in the choroid. Some expression is also found in RGC, INL layer of retina, ONH, sclera, cornea endothelial and stroma; and ciliary body.

METHODS : To visualize the BRB _in vivo, _we utilized the transgenic _Tg(l-fabp:DBP-EGFP) _zebrafish model that expresses vitamin D binding protein (a member of the albumin gene family) tagged to GFP. This model displays the integrity of the BRB with GFP-tagged protein localized within the retinal vasculature by 3 days post-fertilization. Breakdown of the BRB is visualized as “leaking” of GFP outside the vasculature.

RESULTS : Cell clustering revealed that Myrf deficiency altered cell type distributions with reductions in RPE cells at all timepoints. Cell cycle dynamics were stable, consistent with increased cell death in mutants. There was also a compensatory increase in retinal progenitor (RPC) population at P0, without alteration in overall cell cycle dynamics. Differential gene expression analysis and PANTHER gene ontology-term analysis revealed down regulation of key pathways in mutant RPE cells, including melanosome biogenesis, cytoskeleton, and extracellular matrix.

METHODS : _MgpCre+/-_ mice were bred with _tfap2b+/-_ mice. Male _MgpCre+/-;tfap2b+/- _offspring were then crossed with female _tfap2blox/lox_ mice to obtain the final offspring, the _MgpCre+/-;tfap2b-/lox_ or AP-2β trabecular meshwork region knockout (TMR-KO) mice, as well as littermate controls. A 40 kDA FITC-conjugated dextran tracer was injected into the anterior segment of mutant and control mice. 0.005% LTP eye drops were used for topical treatment of the eye. The mice were euthanized 10 minutes after injection and eyes were enucleated, fixed, and cryosectioned.