From ced5e1abdab21cc6325c61b0b0b309967ff752fd Mon Sep 17 00:00:00 2001 From: Bernie Mulvey Date: Thu, 5 Dec 2024 12:04:09 -0600 Subject: [PATCH] Update index.html --- index.html | 346 +++++++++++++++++++++++++++++++---------------------- 1 file changed, 204 insertions(+), 142 deletions(-) diff --git a/index.html b/index.html index b2d0dc701..21c6a1162 100644 --- a/index.html +++ b/index.html @@ -1,17 +1,15 @@ + + - + + + - - - - - - -Integration of single-nucleus and spatial transcriptomics reveals the molecular landscape of the human hippocampus +index - + - + +
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Integration of single-nucleus and spatial -transcriptomics reveals the molecular landscape of the human -hippocampus

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Overview

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Welcome to the spatial_HPC project! In this study, we -generated spatially-resolved transcriptomics (SRT) and single-nucleus -RNA-sequencing (snRNA-seq) data from adjacent tissue sections of the -anterior human hippocampus across ten adult neurotypical donors. SRT -data was generated using 10x -Genomics Visium (n=36 capture areas) and 10x -Genomics Visium Spatial Proteogenomics (SPG) (n=8 -capture areas). snRNA-seq data was generated using 10x -Genomics Chromium (n=26 total snRNA-seq -libraries).

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If you tweet about this website, the data or the R package please use -the #spatial_HPC hashtag. You can find previous tweets that -way as shown -here.

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Thank you for your interest in our work!

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Spatially-resolved molecular sex differences at single cell +resolution in the adult human hypothalamus

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DOI PENDING

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Study Design

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The hypothalamus is a critical brain area underlying functions with +inherent sex differences, such as reproductive physiology, endocrine +signaling, and metabolism. In the rodent, these sex-differentiated +functions correspond to differences in volume, cell type composition, +and gene expression between males and females across individual +hypothalamic regions (here, “domains”). The ventromedial hypothalamus +(VMH) and arcuate nucleus (ARC) are two hypothalamic regions that +influence appetitive/social behaviors and growth/metabolism, +respectively. While molecular profiling studies in the rodent +hypothalamus have identified specialized cell types with unique +transcriptomic signatures, there is a paucity of data describing the +molecular architecture of the human HYP, especially in the context of +sex-differentiated cell types that drive evolutionarily essential, +hypothalamus-mediated behaviors in males and females.

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This study, led by Bernard (Bernie) Mulvey, Kristen Maynard, and +Kasper Hansen, profiled the adult human mediobasal hypothalamus +(ventromedial nucleus, VMH, and arcuate nucleus, ARC) using Visium and +Xenium spatial transcriptomic platforms (10x Genomics). Atlasing and +sex-differential expression efforts using Visium data from 8 donors (4 +per sex) were used to guide gene selection for subsequent Xenium assays +on adjacent tissue sections from these same 8 donors.

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+Experimental Overview +
Experimental Overview
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Study design

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Experimental design to generate paired single-nucleus RNA-sequencing -(snRNA-seq) and spatially-resolved transcriptomics (SRT) data in the -human hippocampus. (A) Postmortem human tissue blocks from the anterior -hippocampus were dissected from 10 adult neurotypical brain donors. -Tissue blocks were scored and cryosectioned for snRNA-seq assays (red), -and placement on Visium slides (Visium H&E, black; Visium Spatial -Proteogenomics (SPG), yellow). (B) 10ξm tissue sections from all ten -donors were placed onto 2-5 capture areas to include the extent of the -HPC(n=36 total capture areas), for measurement with the 10x Genomics -Visium H&E platform. (C) 10ξm tissue sections from two donors were -placed onto 4 capture areas (n=8 total capture areas) for measurement -with the 10x Genomics Visium-SPG platform. (D) Tissue sections (2-4 -100ξm cryosections per assay) from all ten donors were collected from -the same tissue blocks for measurement with the 10x Genomics 3’ gene -expression platform. For each donor, we sorted on both and PI+NeuN+ -(n=26 total snRNA-seq libraries). (This figure was created with Biorender)

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Examining 13 Xenium samples revealed 5 ARC and 4 VMH neuronal +populations governing known hypothalamus-specific functions and defined +their spatial distributions. Examinining the full dataset of 23 samples, +human VMH and ARC demonstrated increases in retinoid pathway gene +expression relative to mouse. Sex-DE analyses of VMH and ARC revealed +correlated autosomal expression differences, which were localized to +ESR1- and TAC3-expressing neurons in the ARC, and +CRHR2-expressing neurons in the VMH. VMH- and ARC-residing cell +types have a striking number of sex-DE genes linked to sex-biased +disorders, including autism, depression, and schizophrenia. By mapping +disease associations to hypothalamic regions containing cell types with +established roles in mediating sex-divergent physiology and behavior, +these data provide insights into mechanistic bases of sex bias in +neurodevelopmental and neuropsychiatric disorders.

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Sex DE Analysis with Xenium Sex-DE analysis was performed +at the level of Xenium clusters by first subsetting to all cells within +the boundaries of the VMH or ARC. Then, cells of each type are tested +separately for sex-DE within that domain. Thus, broadly distributed cell +clusters/types (e.g., glia) are tested for sex-DE in each domain. +Meanwhile, sex-DE testing of domain-specific neuronal clusters +(e.g., TAC3-ESR1 in ARC) is filtered to the cells +given that label and found in their domain (i.e. in the expected +anatomic space). This simplified schematic only shows one +domain-specific cluster each for ARC and VMH.

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Interactive Websites

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All of these interactive websites are powered by open source -software, namely:

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We provide the following interactive websites, organized by dataset -with software labeled by emojis:

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Data Access

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All data, including raw FASTQ files and -SpaceRanger/CellRanger processed data outputs, -can be accessed via Gene Expression Omnibus (GEO) under accessions GSE264692 -(SRT) and GSE264624 -(snRNA-seq).

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The spatially-resolved transcriptomics (SRT) and single-nucleus RNA-sequencing (snRNA-seq) data can also be accessed through the bioconductor -package at humanHippocampus2024 +

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Supplemental Data S1-S6 and smFISH microscopy
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Supplemental data mentioned in the manuscript, along with smFISH +images on Visium/Xenium-adjacent tissue for LAMP5 and KISS1, are +available through are available through http://research.libd.org/globus/ +via the Globus endpoint jhpce#HYP_suppdata. Readme files for these data +are also available through the endpoint.

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Contact

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We value public questions, as they allow other users to learn from -the answers. If you have any questions, please ask them at LieberInstitute/spatial_hpc/issues -and refrain from emailing us. Thank you again for your interest in our -work!

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Further data availability
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FASTQ files from Visium and unfiltered sample-level xeniumranger 1.7 +outputs (transcript-level data) compatible with Xenium Explorer software +are respectively available through GEO accessions GSE280316 +and GSE280460. +Addditional processed data may be added to the Globus endpoint in the +process of review and publication.

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Internal

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  • JHPCE location: -/dcs04/lieber/lcolladotor/spatialHPC_LIBD4035/spatial_hpc
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Files:

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  • code: Scripts for running all analyses.
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  • plots: plots generated by analysis scripts.
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    • Images: images used for running -SpaceRanger and VistoSeg.
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    • spaceranger: SpaceRanger output -files.
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    • sample_info: metadata about samples.
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  • snRNAseq_HPC: code, plots, and data for snRNA-seq -analyses.
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  • Code for running GraphST -clustering pipeline can be found here: https://github.com/JianingYao/SpatialHPC_graphST_multipleSample
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This GitHub repository is organized along the R/Bioconductor-powered -Team Data Science group guidelines. It follows the LieberInstitute/template_project -structure.

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How to Cite

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PENDING

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Files:

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