瑞典隆德大学Tariq Enver、Els Mansell等研究人员合作发现，线粒体增强可改善造血干细胞功能中与年龄有关的异质性。相关论文于2020年10月20日在线发表在《细胞—干细胞》杂志上。

Title: Mitochondrial Potentiation Ameliorates Age-Related Heterogeneity in Hematopoietic Stem Cell Function

Author: Els Mansell, Valgardur Sigurdsson, Elitza Deltcheva, John Brown, Chela James, Kenichi Miharada, Shamit Soneji, Jonas Larsson, Tariq Enver

Issue&Volume: 2020-10-20

Abstract: Aging is associated with reduced fitness and increased myeloid bias of the hematopoietic stem cell (HSC) compartment, causing increased risk of immune compromise, anemia, and malignancy. We show that mitochondrial membrane potential (MMP) can be used to prospectively isolate chronologically old HSCs with transcriptional features and functional attributes characteristic of young HSCs, including a high rate of transcription and balanced lineage-affiliated programs. Strikingly, MMP is a stronger determinant of the quantitative and qualitative transcriptional state of HSCs than chronological age, and transcriptional consequences of manipulation of MMP in HSCs within their native niche suggest a causal relationship. Accordingly, we show that pharmacological enhancement of MMP in old HSCs in vivo increases engraftment potential upon transplantation and reverses myeloid-biased peripheral blood output at steady state. Our results demonstrate that MMP is a source of heterogeneity in old HSCs, and its pharmacological manipulation can alter transcriptional programs with beneficial consequences for function.

DOI: 10.1016/j.stem.2020.09.018

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30493-8