Medhealth Review

A New Method to Study Bone Marrow Microenvironment Precisely

A detailed molecular analysis of the bone marrow microenvironment revealed that the cells that control blood stem cell maintenance are more diverse than previously thought, and that they most likely share traits that are conserved across species.

Using advanced bioinformatics, an international research team discovered the complexity and high level of conservation of the bone marrow (BM) microenvironment that regulates blood stem cells.

Blood stem cells have the ability to differentiate and regenerate into various types of blood cells, including white blood cells, red blood cells, and platelets. The microenvironment, or “niche” in the BM where blood stem cells are located, controls their self-renewal and differentiation. However, little is known about the niche’s cellular makeup and the various tasks that each of its component parts perform.

KAUST (King Abdullah University of Science and Technology) bioinformatician and computational biologist David Gomez-Cabrero stated, “We don’t yet understand the composition of the BM niche and how it integrates local and systemic inputs to regulate hematopoiesis.”

To better understand cellular identity and function, Gomez-Cabrero has been developing new methods for combining single-cell sequencing datasets. Scientists can precisely profile the genes, proteins, and metabolites in individual cells thanks to single-cell technologies.

Gomez-Cabrero focused on endothelial and mesenchymal stromal cells, two cell types required for blood stem cell maintenance, in an integrative analysis of three different mouse BM niche datasets. 

The authors of the study integrated single-cell gene expression data (single-cell RNA sequencing) for each of these cell types to demonstrate the heterogeneity of these niche cells and identify various cellular subtypes and molecular states. Each subtype is determined by the expression of a specific set of genes that provides information about the function and stage of cell differentiation. In total, they discovered 11 mesenchymal subclusters and 14 endothelial subclusters.

When mouse and human BM samples were compared, certain subcluster gene signatures and recognised niche factors controlling hematopoiesis were found to be conserved. According to Gomez-Cabrero, this suggests that the biological processes that define the BM microenvironment are likely shared by a variety of species.

To better understand the composition and regulation of cells in the BM microenvironment and their interactions, Gomez-Cabrero and colleagues Borja Saez and Felipe Prosper will continue to incorporate new data modalities into their analyses, such as epigenetics, proteomics, and imaging data.

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