Group Leader Biogipuzkoa Health Research Institute San Sebastian, Pais Vasco, Spain
Abstract: Identification of stemness proteins is a cornerstone of stem cell biology. Several attempts have been made to search for stemness genes using transcriptomics with controversial results. We applied a proteomics approach to identify stemness proteins based on label-free quantitative mass spectrometry. Our results bridge previous transcriptomics approaches and show the significant relevance of DNA repair and helicase activity of stemness proteins located not only in the nucleus, but also in the mitochondrion and cilium. Synteny analysis revealed potential stemness hot spots in the G-bands D2.2 of chromosome 4 and D2 and A3.3 of chromosome 17. Our results provide a different set of stemness markers than previously published work that relied on transcriptome analysis. Although our stemness markers differed from transcriptomics approaches, we found similar functions and chromosome hot spots. We can see our stemness proteins as a bridge connecting the stemness genes found in the previous transcriptomics studies. There is an apparent paradox in the fact that different cell lineages with stem cell properties do not share a meaningful set of genes. We conclude that different stem cell populations use different regulatory networks to achieve their stem state, suggesting that stemness is not a universal property. Nevertheless, the proteomic measurements show that there are some common proteins involved in DNA repair and transcriptional activities that are shared by all stem cell lineages analyzed. Thus, although high-throughput techniques may not be able to reveal a universal stemness simply due to the possible non-existence of such a universal network, the convergence of our functional proteomics results with the previous transcriptomics results reveals the existence of a functional and synteny stemness signature. Thus, our approach sheds new light on the stemness search problem, where the proteomics measurements provide a synergetic view to the transcriptomics approaches.
Funding Source: M.J.A.-B. was supported by Ministerio de Ciencia e Innovación, Spain Grant No. PID2023-152752OB-I00/AEI/10.13039/501100011033.
