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Analysis of microisolated frontal cortex excitatory layer III and V pyramidal neurons reveals a neurodegenerative phenotype in individuals with Down syndrome

GSE251939 Homo sapiens (human) RNA-seq (gene expression) 82 samples Submitted 2024/08/07 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 82 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
82 samples: 82 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Analysis of microisolated frontal cortex excitatory layer III and V pyramidal neurons reveals a neurodegenerative phenotype in individuals with Down syndromeActa neuropathologica · 2024
Summary (written by the submitters)
Down syndrome (DS) is the most prevalent genetic abnormality, occurring in ~1/700 live births caused by triplication of human chromosome 21 (HSA21). DS individuals have a multitude of phenotypic changes in peripheral systems and most notably, are cognitively impaired, with deficits in learning, language and memory acquisition and consolidation.
Read the full summary ↓
Further, individuals with DS develop Alzheimer’s disease (AD) pathology during early middle-age (mid-30’s), although the underlying mechanism(s) driving this pathology onset are not well understood. Contributing to cognitive impairment in DS, morphological deficits are present in cortical lamination and distribution, with Layer III (L3) and Layer V (L5) pyramidal neurons showing reduced proliferation and a disorganized laminar structure. As such, examining cortical L3 and L5 pyramidal neurons in DS individuals with AD pathology may elucidate alternate driver mechanisms of disease onset. We examined DS and age-matched control (CTR) brains from individuals without intellectual disabilities or dementia using postmortem frontal cortex (BA9) via single population low input RNA-sequencing. We specifically targeted L3 and L5 pyramidal neurons to understand circuitry-based alterations in DS/AD individuals to elucidate mechanistic drivers of disease pathology. We show convergent and divergent gene expression changes in L3 and L5 pyramidal neurons which may underlie cognitive deficits and degenerative pathology associated with aging in the DS brain. We pinpoint alterations in HSA21 gene expression as well as a multitude of convergent differentially expressed genes (DEGs) and relevant pathways via bioinformatic inquiry in the DS brains that underlie mechanisms of degeneration. Distinctly, convergent gene expression reveals a neurotoxic phenotype, with multiple canonical pathways of dysregulation and disease functions linked to the convergent DEGs, including downregulation of the CLEAR signaling pathway and significantly increased activation of the neuroinflammation signaling pathway. We identify several target genes including mitogen activated protein kinase 1 and 3 (MAPK1/3), calcium voltage-gated channel subunit alpha1 A (CACNA1A) and superoxide dismutase 1 (SOD1), which exhibit overlap in multiple pathways and disease functions and/or display dysfunctional protein-protein network interactions for further examination. Novel targets identified by our single population approach in L3 and L5 pyramidal neurons may be drivers of the disease mechanism and therefore may be therapeutic candidates for amelioration of degenerative pathology that targets memory and executive function circuits in DS/AD.
Published in
Analysis of microisolated frontal cortex excitatory layer III and V pyramidal neurons reveals a neurodegenerative phenotype in individuals with Down syndrome
Alldred MJ, Pidikiti H, Ibrahim KW et al. · Acta neuropathologica 2024 · PMID 39105932 · doi:10.1007/s00401-024-02768-0
This dataset
Open GSE251939 in finder → Find more human RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE251939_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1055954 and SRA study SRP479728. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39105932) ↗
Study design
82 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 82 sample titles: 82 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

+ 42 more — browse all 82 samples with per-sample file links →

Datasets on a similar topic

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