GEO series

Combinatorial BMP4 and Activin direct choice between alternate routes to endoderm during human gastrulation [RN25025_RNAseq]

GSE296029 Homo sapiens (human) Single-cell RNA-seq 15 samples Submitted 2025/10/01 Platform GPL34281

At a glance

Single-cell RNA-seq · human · 15 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: 15 samples: 5 conditions, mostly in triplicateGroups 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: Combinatorial BMP4 and activin direct the choice between alternate routes to endoderm in a stem cell model of human gastrulationDevelopmental cell · 2025

Summary (written by the submitters)

Cellular differentiation requires the proper interpretation of multiple signalling cues which vary in concentration. How exactly the combination and history of signals a cell is exposed to influences a fate decision remains poorly understood. In this study we use hESCs as a tractable model system to explore how combinations of cues guide state transitions during gastrulation.

Read the full summary ↓

Using single-cell transcriptomics and live-cell imaging of engineered hESCs expressing endogenous cell state reporters, we reconstructed developmental lineages and obtained single-cell measurements of fate specification dynamics during gastrulation. We found that definitive endoderm, one of the three germ layers, arises from two distinct developmental trajectories: a direct route from pluripotency, and an indirect route via a mesoderm progenitor state. Furthermore, by modulating the signalling input we found that the relative concentration of Activin and BMP4 controls the choice between alternate trajectories to endoderm. These findings reveal a lineage convergence event during human gastrulation with multiple routes existing to definitive endoderm dictated by the combination of signalling cues presented. This work shows that the combination cues a cell is exposed to not only directs the final fate outcome it assumes, but the developmental route taken.

Published in

Combinatorial BMP4 and activin direct the choice between alternate routes to endoderm in a stem cell model of human gastrulation

Inge OCK, Copin E, Cornwall-Scoones J et al. · Developmental cell 2025 · PMID 40930099 · doi:10.1016/j.devcel.2025.08.009

This dataset

Open GSE296029 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 GSE296029_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 PRJNA1257352 and SRA study SRP582405. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40930099) ↗

Study design

5 conditions, mostly in triplicate

mTeSR1 ×3 SOX17-Achilles ×3 SOX17+Achilles+ ×3 SOX17-Achilles+ ×3 SOX17+Achilles ×3

Supports a between-group comparison across 15 samples.

How we read this: 5 replicated groups read from 15 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

GSM8963652 mTeSR1_R1 mTeSR1
GSM8963653 SOX17-Achilles-_R1 SOX17-Achilles
GSM8963654 SOX17+Achilles+_R1 SOX17+Achilles+
GSM8963655 SOX17-Achilles+_R1 SOX17-Achilles+
GSM8963656 SOX17+Achilles-_R1 SOX17+Achilles
GSM8963657 mTeSR1_R2 mTeSR1
GSM8963658 SOX17-Achilles-_R2 SOX17-Achilles
GSM8963659 SOX17+Achilles+_R2 SOX17+Achilles+
GSM8963660 SOX17-Achilles+_R2 SOX17-Achilles+
GSM8963661 SOX17+Achilles-_R2 SOX17+Achilles
GSM8963662 mTeSR1_R3 mTeSR1
GSM8963663 SOX17-Achilles-_R3 SOX17-Achilles
GSM8963664 SOX17+Achilles+_R3 SOX17+Achilles+
GSM8963665 SOX17-Achilles+_R3 SOX17-Achilles+
GSM8963666 SOX17+Achilles-_R3 SOX17+Achilles

Datasets on a similar topic

GSE274723 Combinatorial BMP4 and Activin direct choice between alternate routes to endoderm during human gastrulation. 72 samples shares bmp4, combinatorial, gastrulation, alternate, endoderm, activin, direct
GSE274677 Combinatorial BMP4 and Activin direct choice between alternate routes to endoderm during human gastrulation [RNA-seq] 51 samples shares bmp4, combinatorial, gastrulation, alternate, endoderm, activin, direct
GSE274676 Combinatorial BMP4 and Activin direct choice between alternate routes to endoderm during human gastrulation [scRNA-seq] 6 samples shares bmp4, combinatorial, gastrulation, alternate, endoderm, activin, direct
GSE286120 Modeling human gastrulation and secondary yolk sac formation with BMP4 signaling center 6 samples shares bmp4, gastrulation
GSE275856 Optogenetic-Programmable Human Embryo Models Elucidate the Interplay Between Tissue Architecture and BMP4 Signaling at the Onset of Gastrulation 2 samples shares bmp4, gastrulation
GSE273465 Rapid Human Oogonia-like Cell Specification via Combinatorial Transcription Factor-Directed Differentiation [RNA-seq] 28 samples shares combinatorial, direct
GSE243362 Electro-assisted cell printing directs in vitro gastrulation and epiblast-like morphogenesis from human pluripotent stem cells 8 samples shares gastrulation, direct
GSE294833 Electro-assisted cell printing directs in vitro gastrulation and epiblast-like morphogenesis from human pluripotent stem cells II 4 samples shares gastrulation, direct

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