A transcriptome atlas of the mouse iris at single cell resolution defines cell types and the genomic response to pupil dilation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA761687 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15813350_1.fastq.gz | Fastqsanger.gz | |||
| SRR15813350_2.fastq.gz | Fastqsanger.gz | |||
| SRR15813352_1.fastq.gz | Fastqsanger.gz | |||
| SRR15813352_2.fastq.gz | Fastqsanger.gz | |||
| SRR15813353_1.fastq.gz | Fastqsanger.gz |
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Project description:Single nuclei RNAseq, in situ hybridization, and immunohistochemistry were used to study the cells comprising the mouse iris in its different functional states.
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Project description:The iris controls the level of retinal illumination by controlling pupil diameter. It is a site of diverse ophthalmologic diseases and it is a potential source of cells for ocular auto-transplantation. The present study provides foundational data on the mouse iris based on single nucleus RNA sequencing. More specifically, this work has (1) defined all of the major cell types in the mouse iris and ciliary body, (2) led to the discovery of two types of iris stromal cells and two types of iris sphincter cells, (3) revealed the differences in cell type-specific transcriptomes in the resting vs. dilated states, and (4) identified and validated antibody and in situ hybridization probes that can be used to visualize the major iris cell types. By immunostaining for specific iris cell types, we have observed and quantified distortions in nuclear morphology associated with iris dilation and clarified the neural crest contribution to the iris by showing that Wnt1-Cre-expressing progenitors contribute to nearly all iris cell types, whereas Sox10-Cre-expressing progenitors contribute only to stromal cells. This work should be useful as a point of reference for investigations of iris development, disease, and pharmacology, for the isolation and propagation of defined iris cell types, and for iris cell engineering and transplantation.
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Project description:The mammalian brain consists of millions to billions of cells that are organized into numerous cell types with specific spatial distribution patterns and structural and functional properties. An essential step towards understanding brain function is to obtain a parts list, i.e., a catalog of cell types, of the brain. Here, we report a comprehensive and high-resolution transcriptomic and spatial cell type atlas for the whole adult mouse brain. The cell type atlas was created based on the combination of two single-cell-level, whole-brain-scale datasets: a single-cell RNA-sequencing (scRNA-seq) dataset of ~7 million cells profiled (~4.0 million cells passing quality control), and a spatially resolved transcriptomic dataset of ~4.3 million cells using MERFISH. The atlas is hierarchically organized into four nested levels of classification: 34 classes, 338 subclasses, 1,201 supertypes and 5,322 clusters. We present a newly developed online platform, Allen Brain Cell (ABC) Atlas, to visualize the mouse whole brain cell type taxonomy and atlas along with the scRNA-seq and MERFISH data and metadata sets. We systematically analyzed the neuronal, non-neuronal, and immature neuronal cell types across the brain and identified a high degree of correspondence between transcriptomic identity and spatial specificity for each cell type. The results reveal unique features of cell type organization in different brain regions, in particular, a dichotomy between the dorsal and ventral parts of the brain: the dorsal part contains relatively fewer yet highly divergent neuronal types, whereas the ventral part contains more numerous neuronal types that are more closely related to each other. We also systematically characterized cell-type specific expression of neurotransmitters, neuropeptides, and transcription factors. The study uncovered extraordinary diversity and heterogeneity in neurotransmitter and neuropeptide expression and co-expression patterns in different cell types across the brain, suggesting they mediate myriad modes of intercellular communications. Finally, we found that transcription factors are major determinants of cell type classification in the adult mouse brain and identified a combinatorial transcription factor code that defines cell types across all parts of the brain. The whole-mouse-brain transcriptomic and spatial cell type atlas establishes a benchmark reference atlas and a foundational resource for deep and integrative investigations of cellular and circuit function, development, and evolution of the mammalian brain.
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Project description:The anterior segment of the eye consists of the cornea, iris, ciliary body, crystalline lens and aqueous humor outflow pathways. Together, these tissues are essential for the proper functioning of the eye. Disorders of vision have been ascribed to defects in all of them; some, including glaucoma and cataract, are among the most prevalent causes of blindness. To characterize the cell types that comprise these tissues, we generated an anterior segment cell atlas of the human eye using high throughput single-nucleus RNA sequencing (snRNAseq). We profiled 191,992 single nuclei from non-diseased anterior segment tissues from 6 human donors, identifying >60 cell types. Many are discrete, whereas others in lens and cornea form continua, corresponding to known developmental transitions that persist in adulthood. Having profiled each tissue separately, we performed an integrated analysis of the entire anterior segment revealing that some cell types are unique to single structure whereas others are shared across tissues. This integrated cell atlas was then used to investigate cell type-specific expression patterns of more than >900 human ocular disease genes identified either through Mendelian inheritance patterns or genome-wide association studies (GWAS).
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Project description:The cerebellar cortex is a well-studied brain structure with diverse roles in motor learning, coordination, cognition and autonomic regulation. However, a complete inventory of cerebellar cell types is currently lacking. Here, using recent advances in high-throughput transcriptional profiling1-3, we molecularly define cell types across individual lobules of the adult mouse cerebellum. Purkinje neurons showed considerable regional specialization, with the greatest diversity occurring in the posterior lobules. For several types of cerebellar interneuron, the molecular variation within each type was more continuous, rather than discrete. In particular, for the unipolar brush cells-an interneuron population previously subdivided into discrete populations-the continuous variation in gene expression was associated with a graded continuum of electrophysiological properties. Notably, we found that molecular layer interneurons were composed of two molecularly and functionally distinct types. Both types show a continuum of morphological variation through the thickness of the molecular layer, but electrophysiological recordings revealed marked differences between the two types in spontaneous firing, excitability and electrical coupling. Together, these findings provide a comprehensive cellular atlas of the cerebellar cortex, and outline a methodological and conceptual framework for the integration of molecular, morphological and physiological ontologies for defining brain cell types.
| S-EPMC8494635 | biostudies-literature
Project description:The human iris tissue is a thin, circular structure in the eye and it is made up of a pigmented epithelial structure. It is a protected internal organ of the eye, located behind the cornea and the aqueous humour. Iris serves main function to control the diameter, size of the pupil and regulation of light exposure to the internal eye structures. Damage or absent iris always results in allowing excess amount of light into the eye which causes medical problem for the patient and also a psychological problem due to strange eye with black hole. A damaged or congenitally defective iris does not function well which results in poor quality of vision. Although different efforts have been made to elucidate the different parts of the human eye proteome in depth, the protein composition of the human iris tissue remains largely unexplored. We have performed a comprehensive analysis of the human iris tissue employing protein and peptide fractionation methods followed by LC-MS/MS identifying 4918 proteins. Bioinformatics analysis revealed that protein components of the iris tissue participated in a plethora of biological process highlighting cell signal transduction, communication, metabolism, energy pathways protein metabolism cell growth and maintenance, transport and immune response activities. We also compared the proteins of iris tissue with high throughput studies on other parts of eye and plasma proteome, which resulted in identifying proteins unique to iris. To our knowledge, this study is the first attempt to profile the global proteome of the human iris tissue. Taken together, these results increase our knowledge about the molecular composition of the human iris tissue and may be useful to understand the molecular basis of the iris and the baseline proteome described in this study should serve as a resource for future research in iris tissue
2022-02-23 | PXD001299 | Pride