October 24, 2022
Novel approaches to resolve the blood stem cell niche
Owen Tamplin PhD
Department of Cell and Regenerative Biology
University of Wisconsin-Madison
Hematopoietic stem and progenitor cells (HSPCs) reside in complex microenvironment made up of many different cell types. An understanding of the signals and communication between HSPCs and their niche is critical for improving curative treatments for blood cancers and disease. We are applying new technologies to reveal novel aspects of the endogenous HSPC niche, including spatial distribution of metabolites, and the complete ultrastructure at nanometer resolution. For example, we are using Imaging Mass Spectrometry (IMS) to analyze the localization of gamma-aminobutyric acid (GABA) that is produced in the mammalian bone marrow. We have shown that GABA has a specific requirement in regulation of HSPCs and their differentiation towards the B cell lineage. GABA is spatially enriched in the endosteum of the bone marrow, which is considered a subdomain of the niche that favors B cell production. In another project, we are using Correlative Light and Electron Microscopy (CLEM) to integrate different imaging modalities. We are using light sheet and confocal microscopy to image fluorescently labeled HSPCs in their niche in transgenic zebrafish embryos. We then process the same embryos for serial section blockface electron microscopy, a technique that creates a massive 3D volume of electron microscopy data for an entire tissue. Using software to align the light and electron microscopy datasets, we can correlate the positions of single HSPCs, and identify all neighboring niche cells and their subcellular contacts with the HSPCs. This has allowed identification of cell types that were not previously known to contribute to the HSPC niche. Together, these new technologies are providing unique spatial maps of HSPCs niches and are changing our view of HSPC regulation.