Haematopoietic stem cells (HSCs) are responsible for continuous renewal of blood and immune cells, capable of both self-renewal and differentiation into effector cells. The balance of these processes is critical for a healthy blood supply, with imbalances (as well as mutations) the underlying causes in a wide range of haematological diseases and leukemias.
HSCs have wide therapeutic potential; they and their progenitors have consequently been extensively characterised at genomic and transcriptomic levels. However, mRNA detection is not a reliable measure of protein presence, with frequent poor correlation of mRNA and protein abundance well documented. Better understanding the proteomic profiles of these cell types would allow for deeper insight into stem cell and progenitor biology.
Rare and frequently difficult to purify, HSCs present challenges for traditional proteomics methods, limiting the scope of previous studies. To overcome this, Zaro et al utilise the Bruker timsTOF Pro mass spectrometer operated in PASEF mode combined with IonOpticks Aurora Series Columns to increase sensitivity and improve proteomic coverage from low-abundant cell types.
The result: an unbiased, characterisation of the young and old adult mouse haematopoietic proteome to levels not previously achieved – 12 cell types in total. Additionally, a subset of genes appears to show post-transcriptional repression.
These results aid greater understanding of the proteomics of normal HSCs and each step of differentiation which, together with transcriptomics, will help reveal how these variations lead to a wide range of human diseases. Further, there are implications to understand mechanisms for stem cell maintenance, niche interactions and fate determination more widely, given most tissues and organs maintain cell numbers via tissue-specific stem cells.
Read the full paper
Proteomic analysis of young and old mouse hematopoietic stem cells and their progenitors reveals post-transcriptional regulation in stem cells.
eLife 2020;9:e62210; 25 Nov 2020. doi: https://doi.org/10.7554/eLife.62210
BW Zaro, JJ Noh, VL Mascetti, J Demeter, B George, M Zukowska, GS Gulati, R Sinha, RA Flynn, A Banuelos, A Zhang, AC Wilkinson, P Jackson, IL Weissman
Commentary by Jarrod Sandow, PhD.
About the author
Jarrod has a background in biotechnology and completed his PhD at the Institute of Medical and Veterinary Science in Adelaide. He is a co-inventor of IonOpticks’ core technology and is driven towards developing innovative solutions for the global proteomics research community that will enable scientists and clinicians to discover more from their samples to accelerate advances in biological and medical research.