Single-cell profiling reveals three endothelial-to-hematopoietic transitions with divergent isoform expression landscapes

Journal article

Hemogenic endothelium (HE) is recognized as the origin of all definitive blood cells, including hematopoietic stem cells (HSCs); however, the mechanisms governing the hematopoietic progenitor versus HSC fate choice within the HE remain unknown. Here we combine differentiation assays with full-length single-cell transcriptome data for extra-embryonic yolk sac (YS) and intra-embryonic aorta-gonad-mesonephros (AGM) region HE populations. We identified and localized three differentiation trajectories, each containing a distinct HE subset: erythromyeloid progenitor-primed HE in the YS plexus, lymphomyeloid progenitor-primed HE in large YS arteries and hematopoietic stem and progenitor cell-primed HE in the AGM. Chromatin modifiers and spliceosome components were enriched in AGM HE. This correlated with a higher isoform complexity of the AGM HE transcriptome. Distinct AGM HE-specific isoform expression patterns were observed for a broad range of genes, including stemness-associated factors like Runx1. Our data form a unique resource for studying cell fate decisions in different HE populations.

Authors: Neo, WH; Fadlullah, MZH; Bhatnagar, H; Barone, C; Quattrini, G

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature [academic journals on nature.com]
• Journal: Nature Cardiovascular Research
• Publication date: 2025-11-11
• Acceptance date: 2025-09-30
• DOI: 10.1038/s44161-025-00740-z
• EISSN: 2731-0590
• ISSN: 2731-0590
• Language: English