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Andy Zeng: Mapping single-cell RNA sequencing data across normal and malignant hematopoiesis

uhnresearch.ca

Nov 5, 2024, 18:35

Andy Zeng: Mapping single-cell RNA sequencing data across normal and malignant hematopoiesis

Andy Zeng, MD/PhD Candidate at the University of Toronto, shared on X:

“I’m excited to share an R package that we’ve created for mapping scRNA-seq data across normal and malignant hematopoiesis! We’ve used this to identify hematopoietic stem cells from healthy tissues and map leukemia cells from hundreds of patients.

RNA

If you’ve performed scRNA-seq on leukemia samples, you’ll be know that analysis can be a chaotic process. Inter-patient heterogeneity dominates clustering even after batch correction, and cell type annotation of individual leukemia cells is also really difficult.

RNA

So, we decided to create a scRNA-seq reference atlas with even proportions of primitive stem and progenitor cells and differentiated immune cells. Importantly, we annotated the cells to be concordant with FACS-purified HSPC fractions, as well as highly purified stem cells.

Andy Zeng: Mapping single-cell RNA sequencing data across normal and malignant hematopoiesis

This map can be used to visualize how hematopoiesis becomes distorted in leukemia. We mapped scRNA-seq data from hundreds of AML patients and identified recurrent patterns of AML differentiation. These were linked to underlying genetic mutations.

Andy Zeng: Mapping single-cell RNA sequencing data across normal and malignant hematopoiesis

We’ve also developed a focused map of human B-cell development spanning fetal and post-natal tissues, used to map 89 B-ALL patient samples. While most cells were Pro-B, there was involvement of multipotent cell states in a subset of B-ALL patients.

Our tutorials teach you to map scRNA-seq data from normal and malignant blood samples within minutes.

Alternatives:
I don’t like Azimuth due to low HSPC resolution, but here are some other great atlases:

Single-cell proteo-genomic reference maps of the hematopoietic system enable the purification and massive profiling of precisely defined cell states

An immunophenotype-coupled transcriptomic atlas of human hematopoietic progenitors.”

Andy Zeng: Mapping single-cell RNA sequencing data across normal and malignant hematopoiesis