Profiling cell identity and tissue architecture with single-cell and spatial transcriptomics

Gulati, Gunsagar S.; D’Silva, Jeremy Philip; Liu, Yunhe; Wang, Linghua; Newman, Aaron M.

doi:10.1038/s41580-024-00768-2

Cited by 5 publications

References 288 publications

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Spatiotemporal transcriptomic analyses reveal molecular gradient patterning during development and the tonotopic organization along the cochlear axis

Yan,

Zhang,

Wang

et al. 2024

Preprint

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The cochlea is a highly specialized organ, responsible for auditory functions, yet its development, spatial molecular profiles, and structural basis for hearing function remain poorly understood due to its structural complexity and intricate organization of various cell types. Disruption of cochlear architecture and development process can lead to cochlear malfunction, resulting in hearing defects, including frequency discrimination impairments and hearing loss. In this study, we present the first comprehensive spatiotemporal single-cell atlas of the cochlea, unveiling dynamic gene expression patterns and cellular patterning during development and adulthood. By integrating the spatial transcriptomics, normal single-cell transcriptomics, and RNA in situ detection, our analyses revealed distinct temporal gene expression profiles across the apical, middle, and basal regions of cochlea. Notably, spatial differential gene expression analyses uncovered regional heterogeneity among hair cell and spiral ganglion neuron subtypes, including differences in cell composition, cell-cell interactions, spatial localization. These findings suggest a cellular and molecular basis for sound frequency discrimination and sensitivity gradients along cochlear axis. Our spatiotemporal analyzes of the mouse cochlea provides a valuable resource for inner ear developmental research and offers insights into the structural, cellular, and molecular mechanisms underlying the tonotopic organization in mammals, and how their disrupting can lead to hearing impairment.

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Spatiotemporal transcriptomic analyses reveal molecular gradient patterning during development and the tonotopic organization along the cochlear axis

Yan,

Zhang,

Wang

et al. 2024

Preprint

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In SituSingle-Cell Spatial Profiling of Matrisome Gene Expression in Glioblastoma

De,

Forero,

Sebastian

et al. 2024

Preprint

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Glioblastoma (GBM) is the most common and aggressive primary brain cancer in adults, characterized by robust infiltrative growth and invasion in the neural microenvironment. While various stromal cells including astrocytes, microglia, and vascular cells in the microenvironment communicate with GBM cells to promote growth and invasion, relatively less is known about the other critical component of the tumor stroma: the extracellular matrix (ECM). There are hundreds of ECM genes and affiliated adhesion and signaling components that comprise the brain matrisome; yet, we understand little about (i) the repertoire of matrisome genes and proteins that are expressed in GBM, (ii) the stromal and cancer cells of origin that express the different matrisome factors, and (iii) how these various components are interconnected to drive tumor malignancy. Here, we have used in situ single cell transcriptomics to analyze the spatial expression of nearly 350 genes that comprise the human matrisome. Our efforts have identified several differentially expressed matrisome genes with functions in ECM adhesion and signaling between cancer cells and stromal cells. In addition, matrisome genes with links to low grade glioma pathogenesis and progression to high grade GBM status have been spatially mapped. Collectively, these experiments reveal the single cell origins of differentially expressed ECM biomarkers as well as their spatial expression patterns in malignant brain tumors. These results may lead to new efforts to therapeutically inhibit matrisome components to benefit patients with malignant brain cancer.

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Monitoring in vivo transcription with synthetic serum markers

Watanabe,

Lee,

Harb

et al. 2024

Preprint

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Understanding transcription profiles of living tissues is critical for biology and medicine. However, measurement of the transcript levels is typically done in homogenized tissues post-mortem. Here, we present a new platform that enables non-invasive monitoring of specific mRNA levelsin vivo, without tissue destruction. We achieved this by combining two cutting-edge tools - synthetic serum markers, called Released Markers of Activity (RMAs), and RNA-based sensors of transcription. We call this platform IN-vivo Tracking of ACtive Transcription, orINTACT. In INTACT, when the target mRNA is expressed, the RNA sensor detects it and triggers the production and release of RMA reporters into the blood. Once in blood, the RMAs can be easily measured through a simple blood draw. Our data shows that INTACT can measure transcription of transgenes, as well as endogenous transcripts, such asc-FosorArc, bothin vivoin the brain and in tissue culture. INTACT enables simple measurement of transcript level histories in genetically-targetable cell populations of living animals.

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Profiling cell identity and tissue architecture with single-cell and spatial transcriptomics

Cited by 5 publications

References 288 publications

Spatiotemporal transcriptomic analyses reveal molecular gradient patterning during development and the tonotopic organization along the cochlear axis

Spatiotemporal transcriptomic analyses reveal molecular gradient patterning during development and the tonotopic organization along the cochlear axis

In SituSingle-Cell Spatial Profiling of Matrisome Gene Expression in Glioblastoma

Monitoring in vivo transcription with synthetic serum markers

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