Omics · study · 2026
Embryonic TGF-β signaling instructs long term HSPC clonality and inflammatory landscape
Listed in NCBI GEO
Embryonic hematopoiesis is essential for establishing lifelong blood and immune system function.
Description
During development, hematopoietic stem cells (HSPCs) acquire intrinsic programs that persist into adulthood and can influence disease susceptibility, yet the molecular signals governing these early-life decisions remain poorly understood. Here, we investigated the role of Transforming Growth Factor-β (TGF-β) signaling in regulating HSPC lineage bias and long-term hematopoietic outcomes.
Using the zebrafish model, we found that transient inhibition of TGF-β signaling during a critical developmental window altered HSPC frequency and migration after their emergence from the hemogenic endothelium into the caudal hematopoietic tissue, analogous to the mammalian fetal liver. Single-cell transcriptomic analysis of embryonic HSPCs revealed repression of migration- and cytoskeleton-associated genes alongside increased expression of myeloid/macrophage-related genes following ALK5 inhibition.
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Functionally, early ALK5 blockade reduced macrophage numbers and promoted an M2-like immunosuppressive transcriptional profile. These developmental perturbations produced sustained effects on hematopoietic and immune function into adulthood, including elevated inflammatory responses in the marrow and impaired regenerative capacity after myeloid injury. Together, our findings identify embryonic TGF-β signaling as a key developmental regulator of HSPC fate and immune programming, with potential implications for immune dysfunction and susceptibility to inflammatory disease later in life.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE341nnn/GSE341887 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE341887 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1504447 ncbi.nlm.nih.gov/bioproject/PRJNA1504447 ↗
project · from NCBI GEO
Topics
- Stated by source
- Danio rerio · Expression profiling by high throughput sequencing
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE341887 | 15 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[organism].NCBITaxon:7955 | 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 |