This project aims to uncover molecular and spatial mechanisms that regulate the engraftment potential of hematopoietic stem cells (HSCs), using high-resolution spatial transcriptomics and single-cell CITE-seq data from human fetal liver tissue.
HSCs are essential for cell-based therapies targeting a range of conditions including leukemia, immunodeficiencies, and hemoglobinopathies. However, efforts to expand or genetically modify HSCs ex vivo often reduce their ability to successfully engraft. In contrast, HSCs from the fetal liver exhibit superior engraftment capacity. This project explores the hypothesis that the fetal liver niche provides unique regulatory cues—both molecular and spatial—that help preserve or enhance this engraftment potential.
We are integrating two powerful omics datasets:
- Stereo-seq spatial transcriptomics (500 nm resolution) to capture tissue architecture and spatial gene expression.
- Single-cell CITE-seq (combining RNA and surface protein data) to profile HSC subpopulations at single-cell resolution.
Using these data, we will:
- Identify gene signatures and regulatory pathways associated with high engraftment potential.
- Analyze the spatial organization and signaling microenvironments of fetal liver HSCs.
- Investigate features such as alternative polyadenylation that may impact stem cell function.
All spatial analysis will be conducted using Giotto, our lab’s specialized platform for spatial transcriptomic data.
This internship project is led by Dr. Ruben Dries (Department of Medicine, Boston University) with support from:
- Edward Ruiz – Fetal liver dataset
- Jiaji George Chen – Giotto platform development
- Ongoing collaboration with the Vanuytsel group at the Center for Regenerative Medicine (CreM)