Omics · study · 2026
Commitment of haematopoietic stem cells to erythroid, megakaryocyte and mast cell lineages is accelerated by IL-33 in humans [Multiome]
Listed in NCBI GEO
The understanding of human haematopoiesis has much improved in the last decade.
Description
It is now accepted that lineage commitment decisions already occur at the level of single haematopoietic stem cells (HSCs). It is also thought that the balance of such decisions is highly influenced by stress, inflammation, age or disease.
However, a lack of tractable models that recapitulate human HSC function and blood formation hampers insights into mechanistic understanding. To address this, we developed an in vitro model of the earliest differentiation trajectories of human HSCs to study perturbations at single-cell resolution. Within 5 days, long-term (LT) HSCs (defined by CD19−CD34+CD38−CD45RA−CD49f+CD90+) plated in this model produced progenitors committed to all major blood lineages: myeloid, erythroid (Ery), lymphoid, megakaryocytes (Meg) and mast cells (MC).
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We uncovered a common cultured Ery, Meg and MC progenitor (cMEMP), marked by high expression of IL1RL1, encoding the receptor for IL-33, ST2. When exposed to IL-33, LT-HSCs show accelerated production of cMEMP and further enhanced differentiation towards the Meg, MC and Ery lineages (in vitro and Ery in vivo). This effect is dependent on MAPK signalling downstream of ST2.
In summary our study: i) presents a novel model to study the earliest divisions of human haematopoiesis, ii) reports a common progenitor for Ery, Meg and MC and iii) identifies IL-33 as a novel mediator of the Ery, Meg and MC lineages through cMEMP. This dataset contains LT-HSCs cultured for 5 days ± IL-33 then 10x multiome.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE317nnn/GSE317321 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE317321 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1406734 ncbi.nlm.nih.gov/bioproject/PRJNA1406734 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Genome binding/occupancy profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE317321 | 11 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[method].geo_series_type:genome-binding-occupancy-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |