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A human-specific regulatory mechanism revealed in a preimplantation model [RNA-seq]

GSE296554 Homo sapiens (human) RNA-seq (gene expression) 49 samples Submitted 2025/07/13 Platform GPL34284
At a glance

RNA-seq (gene expression) · human · 49 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
49 samples: 15 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
A human-specific regulatory mechanism revealed in a pre-implantation modelNature · 2025
Summary (written by the submitters)
Stem cell-based human embryo models offer a unique opportunity for functional studies of the human-specific features of development. Here, we genetically and epigenetically manipulate human blastoids, a 3D embryo model of the blastocyst, to investigate the functional impact of HERVK LTR5Hs, a hominoid-specific endogenous retrovirus, on preimplantation development.
Read the full summary ↓
We uncover a pervasive cis-regulatory contribution of LTR5Hs elements to the hominoid-specific diversification of the blastoids’ epiblast transcriptome. Many of the nearly 700 LTR5Hs genomic insertions in the human genome are unique to our own species. We show that at least one such human-specific LTR5Hs element is essential for the blastoid-forming potential via enhancing expression of the primate-specific ZNF729 gene, encoding a KRAB zinc finger protein. ZNF729 binds G/C-rich sequences, extremely abundant at gene promoters associated with basic cellular functions, such cell proliferation and metabolism. Surprisingly, despite mediating recruitment of TRIM28, at many of these promoters ZNF729 acts as a transcriptional activator. Together, our results illustrate how recently emerged transposable elements and genes can confer developmentally essential functions in humans.
Published in
A human-specific regulatory mechanism revealed in a pre-implantation model
Fueyo R, Wang S, Crocker OJ et al. · Nature 2025 · PMID 41034587 · doi:10.1038/s41586-025-09571-1
This dataset
Open GSE296554 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 GSE296554_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 PRJNA1259977 and SRA study SRP583634. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41034587) ↗
Study design
15 conditions, mostly in triplicate
dark_spheres ×4 blastoids ×4 ZNF729-FH_DMSO ×4 ZNF729-FH_3h ×4 ZNF729-FH_24h ×4 LTR5Hs_CARGO_high_c1 ×3 LTR5Hs_CARGO_high_c2 ×3 LTR5Hs_CARGO_high_c3 ×3 +7 more

Supports a between-group comparison across 49 samples.

How we read this: 15 replicated groups read from 49 sample titles; they account for 49 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

+ 9 more — browse all 49 samples with per-sample file links →

Datasets on a similar topic

Search all human RNA-seq datasets in GEO →

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