A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Vascular adhesion protein-1 defines a unique subpopulation of human hematopoietic stem cells and regulates their proliferation
Tekijät: Iftakhar-E-Khuda Imtiaz, Pessia Alberto, Zheng Shuyu, Kankainen Matti, Kontro Mika, Karikoski Marika, Laurila Juha, Gerke Heidi, Tadayon Sina, Hollmén Maija, Tang Jing, Imhof Beat A, Salmi Marko, Jalkanen Sirpa
Julkaisuvuosi: 2021
Journal: Cellular and Molecular Life Sciences
Tietokannassa oleva lehden nimi: Cellular and molecular life sciences : CMLS
Lehden akronyymi: Cell Mol Life Sci
Vuosikerta: 78
Aloitussivu: 7851
Lopetussivu: 7872
ISSN: 1420-682X
eISSN: 1420-9071
DOI: https://doi.org/10.1007/s00018-021-03977-6
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/67815910
Although the development of hematopoietic stem cells (HSC) has been studied in great detail, their heterogeneity and relationships to different cell lineages remain incompletely understood. Moreover, the role of Vascular Adhesion Protein-1 in bone marrow hematopoiesis has remained unknown. Here we show that VAP-1, an adhesin and a primary amine oxidase producing hydrogen peroxide, is expressed on a subset of human HSC and bone marrow vasculature forming a hematogenic niche. Bulk and single-cell RNAseq analyses reveal that VAP-1+ HSC represent a transcriptionally unique small subset of differentiated and proliferating HSC, while VAP-1- HSC are the most primitive HSC. VAP-1 generated hydrogen peroxide acts via the p53 signaling pathway to regulate HSC proliferation. HSC expansion and differentiation into colony-forming units are enhanced by inhibition of VAP-1. Contribution of VAP-1 to HSC proliferation was confirmed with mice deficient of VAP-1, mice expressing mutated VAP-1 and using an enzyme inhibitor. In conclusion, VAP-1 expression allows the characterization and prospective isolation of a new subset of human HSC. Since VAP-1 serves as a check point-like inhibitor in HSC differentiation, the use of VAP-1 inhibitors enables the expansion of HSC.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
