Spatial transcriptome profiling by MERFISH reveals fetal liver hematopoietic stem cell niche architecture

Area of Science:

• Developmental Biology
• Hematopoiesis
• Stem Cell Biology

Background:

• The hematopoietic stem cell (HSC) niche is crucial for blood cell formation.
• While the bone marrow niche is well-studied, the fetal liver niche requires more investigation.
• Understanding the fetal liver microenvironment is key to comprehending early hematopoiesis.

Purpose of the Study:

• To investigate the spatial organization and transcriptional profiles of cells in wild type (WT) and Tet2 knockout (Tet2-/-) fetal livers.
• To identify cell-cell interactions and signaling pathways regulating hematopoiesis in the fetal liver niche.
• To provide a bioinformatic foundation for HSC spatial regulation in the fetal liver.

Main Methods:

• Multiplexed error-robust fluorescence in situ hybridization (MERFISH) was used to analyze spatial organization and gene expression.
• Individual cell transcriptional profiles were examined in WT and Tet2-/- fetal livers.
• Ligand-receptor signaling interactions between neighboring cell types were identified.

Main Results:

• Specific fetal liver cell types exhibit preferential spatial positioning.
• Hematopoietic stem cells (HSCs) are predominantly in direct contact with endothelial cells (ECs).
• Loss of Tet2 increases HSC numbers and upregulates Wnt and Notch signaling in the HSC niche. Arterial and sinusoidal EC subtypes contribute distinct signals.

Conclusions:

• This study provides a detailed map of cell-cell interactions within the fetal liver HSC niche.
• The findings highlight the role of Tet2 in regulating HSC number and niche signaling.
• A comprehensive understanding of fetal liver hematopoiesis regulation is established, offering a foundation for future research.