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Transient SP140 inhibition unlocks hematopoietic stem cell fate from human pluripotent stem cells [scRNA-seq]

GSE287227 Homo sapiens (human) Single-cell RNA-seq 9 samples Submitted 2026/04/27 Platform GPL24676
At a glance

Single-cell RNA-seq · human · 9 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
9 samples: 8 distinct titles, 1 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.
Summary (written by the submitters)
Efficient derivation of transplantable hematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) is constrained by epigenetic silencing. Through a CRISPR/Cas9 screen with a BCL11A-eGFP reporter, we identified epigenetic reader SP140 suppressing hematopoiesis. Transient genetic or pharmacologic inhibition of SP140 in hPSC-derived teratoma and embryoid body cultures promoted robust multilineage hematopoiesis and accelerated production of HSCs with serial transplantability and durable reconstitution in immunodeficient mice.
Read the full summary ↓
Mechanistically, SP140 blockade unlocked transcription at endothelial-to-hematopoietic transition (EHT) loci through topoisomerase 1-dependent chromatin remodeling, activating key hematopoietic and stem cell programs. Transcriptomic analysis showed activation of these regulators upon SP140 inhibition, which was prevented by topoisomerase 1 blockade. CUT&Tag profiling identified SP140 binding at EHT and HSC-specification gene loci. SP140’s function as an epigenetic gatekeeper was conserved in diverse hPSCs and murine embryo models, where its downregulation enhanced physiological HSC emergence. Importantly, selective SP140 inhibition in a chemically defined, scalable protocol enabled rapid in vitro generation of bona fide human HSCs suitable for transplantation. These findings identify transient SP140 inhibition as an effective strategy to overcome epigenetic barriers and unlock clinically relevant HSC specification from hPSCs, advancing regenerative hematopoiesis and cell therapy.
This dataset
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.

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 GSE287227_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1211648 and SRA study SRP557891. Searching any of these in the dataset finder brings you back here.

Study design
8 distinct titles, 1 of them repeated
Teratoma_CD45 ×2

How we read this: Read from 9 sample titles: 8 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
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