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Disordered protein LAT encodes relative levels of signaling pathways in T cell activation [Perturb-CITE-seq]

GSE311572 Homo sapiens (human) Single-cell RNA-seq 22 samples Submitted 2026/04/30 Platform GPL30173
At a glance

Single-cell RNA-seq · human · 22 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart.
Organism
Homo sapiens (human)
Samples
22 samples: 22 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
Disordered protein LAT encodes relative levels of signaling pathways in T cell activationScience (New York, N.Y.) · 2026
Summary (written by the submitters)
Immune cells transduce environmental stimuli into responses essential for host health via complex signaling cascades. T cells, in particular, leverage their unique T cell receptors (TCRs) to detect specific Human Leukocyte Antigen (HLA)-presented peptides. TCR activation is then relayed via linker for activation of T cells (LAT), a TCR-proximal disordered adapter protein, which organizes protein partners and mediates the propagation of signals down diverse pathways including NFAT and AP-1.
Read the full summary ↓
Here, we studied how balanced downstream pathway activation is encoded in the amino acid sequence of LAT. To comprehensively profile the sequence-function relationship of LAT, we developed a pooled, single-cell, high-content screening approach in which a large series of mutants in the LAT protein were analyzed to characterize their effects on T cell activation. Measuring epigenetic, transcriptomic, and cell surface protein dynamics of single cells harboring distinct LAT mutants, we found functional regions spanning over 40% of the LAT amino acid sequence. Conserved sequence motifs for protein interactions, along with charge distribution, are critical sequence features, and contribute to interpretation of human genetic variation in LAT. While mutant defect severity spans from moderate to complete loss of function, nearly all defective mutants, irrespective of their position in LAT, confer balanced defects across the NFAT and AP-1 pathways. To understand the molecular basis for this observation, we performed proximal protein labeling, which demonstrated that disruption of LAT interaction with a single partner protein indirectly disrupts other partner interactions, likely through the dual roles of these proteins as effectors of downstream pathways and bridging factors between LAT molecules. Overall, we report widely distributed functional regions throughout a disordered adapter and a precise physical organization of LAT and interacting molecules which constrains signaling outputs. More broadly, we describe an approach for interrogating sequence-function relationships for proteins with complex activities across regulatory layers of the cell.
Published in
Disordered protein LAT encodes relative levels of signaling pathways in T cell activation
Rubin AJ, Dao TT, Schueppert AV et al. · Science (New York, N.Y.) 2026 · PMID 42060760 · doi:10.1126/science.ads6847
This dataset
Open GSE311572 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 GSE311572_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: 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 PRJNA1369867 and SRA study SRP649179. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42060760) ↗
Study design
22 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 22 sample titles: 22 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
Datasets on a similar topic

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