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CHARTING AND PROBING THE ACTIVITY OF ADARS IN HUMAN DEVELOPMENT AND CELL-FATE SPECIFICATION

GSE248941 Homo sapiens (human) Single-cell RNA-seq 18 samples Submitted 2024/10/24 Platform GPL11154Platform GPL13112
At a glance

Single-cell RNA-seq · human · 18 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Homo sapiens (human)
Samples
18 samples: 6 conditions, mostly in duplicateGroups 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
Charting and probing the activity of ADARs in human development and cell-fate specificationNature communications · 2024
Summary (written by the submitters)
Adenosine deaminases acting on RNA (ADARs) impact diverse cellular processes and pathological conditions. While we possess important insights into their roles in adult tissues, their functions in early cell fate specification remain less understood. To address this, we devised a comprehensive framework to investigate ADARs in human development.
Read the full summary ↓
We began by charting time-course RNA editing profiles in human organs from fetal to adult stages, enabling broad insights into RNA editing trends across diverse tissues. Next, we utilized hPSC differentiation to experimentally probe ADARs across specific tissue-types, harnessing brain organoids as neural specific, and teratomas as pan-tissue developmental models. We found that time-series teratomas faithfully recapitulated developmental trends observed in fetal tissue. Motivated by this, we conducted pan-tissue, single-cell CRISPR-KO screens of ADARs in teratomas to assess their role in cell-fate specification. Knocking out ADAR1 led to a global decrease in RNA editing across all germ-layers. Intriguingly, we observed a significant fitness defect in mesodermal tissues, and an enrichment of adipogenic cells, revealing a novel role for ADAR1 in mesenchymal differentiation. Collectively, we developed a multi-pronged framework charting time-resolved RNA editing profiles in fetal and fetal-like organ tissues, thereby shedding light on the role of ADARs in development and cell fate-specification.
Published in
Charting and probing the activity of ADARs in human development and cell-fate specification
Dailamy A, Lyu W, Nourreddine S et al. · Nature communications 2024 · PMID 39537590 · doi:10.1038/s41467-024-53973-0
This dataset
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.

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 GSE248941_RAW.tar (it can run to tens of gigabytes).

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.

What the files usually look like: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1046489 and SRA study SRP475035. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly in duplicate
ADAR CRISPR-KO screen teratoma ×4 time series teratoma wk10 1 ×3 time series teratoma wk4 1 ×2 time series teratoma wk6 1 ×2 time series teratoma wk8 1 ×2 time series teratoma wk10 2 ×2 time series teratoma wk4 2 ×1 time series teratoma wk6 2 ×1 +1 more

Supports a between-group comparison across 15 samples.

How we read this: 6 replicated groups read from 18 sample titles; they account for 15 of them. 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
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