GEO series

Local source of FGF8 specifies a fronto-temporal axis in engineered human brain organoids (PolarOids)

GSE175592 Homo sapiens (human) RNA-seq (gene expression) 21 samples Submitted 2024/05/03 Platform GPL16791

At a glance

RNA-seq (gene expression) · human · 21 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: 21 samples: 21 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 polarized FGF8 source specifies frontotemporal signatures in spatially oriented cell populations of cortical assembloidsNature methods · 2024

Summary (written by the submitters)

The establishment of the fronto-temporal axis in the developing human cortex is achieved by temporary signaling activity coming from secondary organizers. However, studying this process remains challenging due to the limited access to fetal material and inaccuracy of animal models in mimicking human-specific aspects. Although human brain organoids provide a potential solution to study this, their lack of axial organization does not supply the appropriate positional information needed to recapitulate detailed patterning processes in situ.

Read the full summary ↓

Here, we develop a method that combines a cell line expressing the morphogen FGF8 fused to organoids engineered with PDMS moulds representing the exact length of the developing brain, resulting in the formation of polarized cortical organoids, or PolarOids. Thanks to a dose-sensitive reporter for anterior cortical differentiation, we carefully titrate and time the fusion dynamics to elicit a gradient in the patterned tissue while preserving neural activity as assessed through electrophysiology. We show that our localized FGF8 source is sufficient to trigger a distance-dependent transcriptional signature that matches fronto-temporal cortical fates in vivo. Lastly, we use these PolarOids to model a disease-relevant FGFR3 mutation and describe the transcriptional loss of axial gradient formation underlying a dramatic cortical phenotype observed in patients. As such, Polaroids provide a powerful tool to model hitherto neglected human diseases caused by defects in antero-posterior patterning in the brain

Published in

A polarized FGF8 source specifies frontotemporal signatures in spatially oriented cell populations of cortical assembloids

Bosone C, Castaldi D, Burkard TR et al. · Nature methods 2024 · PMID 39294368 · doi:10.1038/s41592-024-02412-5

This dataset

Open GSE175592 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 GSE175592_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 PRJNA733039 and SRA study SRP321550. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39294368) ↗

Study design

21 samples, each with a distinct title — no replicated groups

Supports a case/control comparison: 9 samples read as cases, 3 as controls.

How we read this: Read from 21 sample titles: 21 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

GSM5342232 PROXIMAL1 (P1)
GSM5342233 MEDIAL1 (M1)
GSM5342234 DISTAL1 (D1)
GSM5342235 PROXIMAL2 (P2)
GSM5342236 MEDIAL2 (M2)
GSM5342237 DISTAL2 (D2)
GSM5342238 PROXIMAL3 (P3)
GSM5342239 MEDIAL3 (M3)
GSM5342240 DISTAL3 (D3)
GSM5342241 CONTROL1 (CTRL1)
GSM5342242 CONTROL2 (CTRL2)
GSM5342243 CONTROL3 (CTRL3)
GSM5342244 MUTANT PROXIMAL1 (PMUT1)
GSM5342245 MUTANT MEDIAL1 (MMUT1)
GSM5342246 MUTANT DISTAL1 (DMUT1)
GSM5342247 MUTANT PROXIMAL2 (PMUT2)
GSM5342248 MUTANT MEDIAL2 (MMUT2)
GSM5342249 MUTANT DISTAL2 (DMUT2)
GSM5342250 MUTANT PROXIMAL3 (PMUT3)
GSM5342251 MUTANT MEDIAL3 (MMUT)
GSM5342252 MUTANT DISTAL3 (DMUT3)

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