GEO series

A stem cell model identifies two alternative cell fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation (scRNA-seq)

GSE277485 Homo sapiens (human) Single-cell RNA-seq 14 samples Submitted 2025/08/15 Platform GPL24676

At a glance

Single-cell RNA-seq · human · 14 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: 14 samples: 12 distinct titles, 2 of them repeatedGroups 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: A stem cell differentiation model reveals two alternative fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiationCommunications biology · 2025

Summary (written by the submitters)

CBFA2T3::GLIS2 (CG) is an oncogenic fusion protein found in high-risk pediatric acute megakaryoblastic leukemia (AMKL). To gain insight into its leukemogenic mechanism, we developed a disease model based on genetically modified human induced pluripotent stem cells. We found that CG expression disrupts myeloid differentiation in this model via two alternate paths: either by delaying differentiation of aberrant megakaryocytes (aMK) or by locking aberrant megakaryocyte progenitors (aMKP) in a proliferative state akin to AMKL tumor cells.

Read the full summary ↓

We characterized the gene-regulatory networks characterizing both cell states by single-cell and epigenome analysis, and observed that CG sustains aMKPs along with cooperators GATA2 and ERG, while repressing differentiation factors like CEBPA, LYL1, and NFE2. In contrast, aMKs maintained many differentiation factors and did not up-regulate regulators of self-renewal. In future, our findings may contribute to improved diagnostic and therapeutic procedures aimed at interconverting cell states in CG-positive patients.

Published in

A stem cell differentiation model reveals two alternative fates in CBFA2T3::GLIS2-driven acute megakaryoblastic leukemia initiation

Shoeb MR, Schinnerl D, Shaw LE et al. · Communications biology 2025 · PMID 40866546 · doi:10.1038/s42003-025-08730-4

This dataset

Open GSE277485 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 GSE277485_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 PRJNA1162503 and SRA study SRP533386. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40866546) ↗

Study design

12 distinct titles, 2 of them repeated

wt ×2 mut ×2

How we read this: Read from 14 sample titles: 12 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

GSM8523149 wt_13
GSM8523150 mut_13
GSM8523151 wt_25
GSM8523152 mut_25
GSM8523153 D115_GEX
GSM8523154 D13_GEX
GSM8523155 D13_plusdTAG_13_GEX
GSM8523156 D25_GEX
GSM8523157 D25_plusdTAG_13_GEX
GSM8523158 D115_CMO
GSM8523159 D13_CMO
GSM8523160 D13_plusdTAG_13_CMO
GSM8523161 D25_CMO
GSM8523162 D25_plusdTAG_13_CMO

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