GEO series

A brain organoid/ALL co-culture model reveals the AP-1 pathway as critically associated with CNS-involvement of BCP-ALL

GSE271998 Homo sapiens (human) RNA-seq (gene expression) 15 samples Submitted 2024/07/16 Platform GPL16791

At a glance

RNA-seq (gene expression) · human · 15 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)
Topic: Acute lymphoblastic leukemiaThis series is part of our curated briefing on it.
Samples: 15 samples: 15 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: A brain organoid/ALL coculture model reveals the AP-1 pathway as critically associated with CNS involvement of BCP-ALLBlood advances · 2024

Summary (written by the submitters)

Central nervous system (CNS) involvement remains a clinical hurdle in treating childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The disease mechanisms of CNS leukemia are primarily investigated using 2D cell culture and mouse models. Given the variations in cellular identity and architecture between the human and murine CNS, it becomes imperative to seek complementary models to study CNS leukemia.

Read the full summary ↓

Here, we present a first-of-its-kind 3D co-culture model combining human brain organoids and BCP-ALL cells. We noticed signicantly higher engraftment of TCF3::PBX1+ leukemia cell lines and patient-derived xenograft (PDX) cells in human induced pluripotent stem cell (iPSC)-derived cerebral organoids when compared to cell lines derived from chronic myeloid leukemia (CML), a subtype typically not associated with CNS involvement. Next, to validate translatability between organoid co-culture model and in vivo murine models, we confirmed that targeting CNS leukemia relevant pathways like CD79a/Igα or CXCR4-SDF1 reduced the invasion of BCP-ALL cells into organoids. RNA sequencing and further validations of organoid-invading leukemia cells compared to the non-invaded fraction revealed significant upregulation of the AP-1 transcription factor-complex members in organoid-invading cells. Moreover, we detected a significant enrichment of AP-1 pathway genes in ALL-PDX cells recovered from the CNS compared to spleen blasts of mice transplanted with TCF3::PBX1+ PDX cells, substantiating the role of AP-1 signaling in CNS disease. Accordingly, we found significantly higher levels of the AP-1-gene JUN in patients initially diagnosed as CNS-positive compared to CNS-negative cases as well as CNS-relapse cases in a cohort of 100 BCP-ALL patients. Our results suggest iPSC-derived brain organoids as a novel model to investigate CNS-involvement and identify the AP-1 pathway as a critical driver of CNS-disease in BCP-ALL.

Published in

A brain organoid/ALL coculture model reveals the AP-1 pathway as critically associated with CNS involvement of BCP-ALL

Gebing P, Loizou S, Hänsch S et al. · Blood advances 2024 · PMID 39008716 · doi:10.1182/bloodadvances.2023011145

This dataset

Open GSE271998 in finder → Find more human RNA-seq datasets → Acute lymphoblastic leukemia landscape →

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 GSE271998_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 PRJNA1134264 and SRA study SRP519206. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39008716) ↗

Study design

15 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 15 sample titles: 15 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

GSM8390485 M915_Sp
GSM8390486 M915_BM
GSM8390487 M915_CNS
GSM8390488 M917_Sp
GSM8390489 M917_BM
GSM8390490 M917_CNS
GSM8390491 M922_Sp
GSM8390492 M922_BM
GSM8390493 M922_CNS
GSM8390494 M1006_Sp
GSM8390495 M1006_BM
GSM8390496 M1006_CNS
GSM8390497 M1011_Sp
GSM8390498 M1011_BM
GSM8390499 M1011_CNS

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GSE271750 A brain organoid/ALL co-culture model reveals the AP-1 pathway as critically associated with CNS involvement of BCP-ALL 12 samples shares bcp-all, ap-1, co-culture, critically, organoid, brain

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