Integrative transcriptomic analysis of developing hematopoietic stem cells in human and mouse at single-cell...

Area of Science:

• Developmental Biology
• Stem Cell Biology
• Genomics

Background:

• Hematopoietic stem cell (HSC) development is crucial for blood formation.
• Mouse models are widely used to study HSC development, assuming evolutionary conservation in humans.
• Single-cell transcriptomic data for cross-species comparison of developmental HSCs is limited.

Purpose of the Study:

• To perform an integrative transcriptomic analysis of key HSC development cell populations in human and mouse embryos.
• To compare the transcriptomic profiles of developmental HSCs at single-cell resolution between humans and mice.
• To identify conserved molecular signatures and evolutionary differences in HSC development.

Main Methods:

• Integrative transcriptomic analysis of single-cell RNA sequencing data.
• Comparison of cell populations including hemogenic endothelial cells, pre-HSCs, and mature HSCs.
• Analysis of samples from human and mouse embryos (AGM region, fetal liver) and adult mouse bone marrow.

Main Results:

• General transcriptomic similarity was observed between corresponding human and mouse HSC development cell populations.
• Human AGM HSPCs with arterial characteristics resembled mouse pre-HSCs.
• Two other human AGM HSPC populations showed similarity to fetal liver HSPCs, suggesting AGM maturation before fetal liver colonization in humans, unlike in mice.

Conclusions:

• Significant transcriptomic conservation exists in critical cell populations and molecular characteristics during HSC development between humans and mice.
• The findings provide a valuable resource and theoretical basis for studying mammalian HSC development and regeneration.
• Differences in maturation timing highlight species-specific nuances in HSC development pathways.