Characterization of the molecular networks governing hematopoietic stem cell expansion

Until recently, attempts to expand blood-forming hematopoietic stem cells (HSCs) ex vivo have largely failed to achieve high yields of functional stem cells in culture settings, thereby compromising research efforts and clinical translation.

In 2019, the laboratories of Drs Yamazaki and Nakauchi published a ground-breaking study which introduced a novel culture system where functional mouse HSCs could be expanded >200 fold.

Although this work represents an unprecedented leap forward in the field of ex vivo HSC expansion, serveral outstanding questions regarding the function an molecular composition of the expanded HSCs remain.

Resolving these questions is absolutely necessary in order to establish best practices for ex vivo expansion of mouse HSCs for research use, as well as for successful translation to human stem cells for research and clinical purposes.

In the proposed project, I aim to characterize the transcriptome, proteome and secretome of ex vivo expanded mouse HSCs, and to link these molecular data to the function of the expanded HSCs using genetic and pharmacological modulation and transplantation experiments.

The combined application of state-of-the-art molecular profiling tools, such as single-cell RNA-sequencing and mass spectrometry-based proteomics, and thorough functional assays will illuminate previously unidentified pathways involved in HSC expansion and set the stage for their rapid translation to human HSCs by our collaborators in the Yamazaki group.