Haematopoietic ageing through the lens of single-cell technologies.

Human lifespan is now longer than ever and, as a result, modern society is getting older. Despite that, the detailed mechanisms behind the ageing process and its impact on various tissues and organs remain obscure. In general, changes in DNA, RNA and protein structure throughout life impair their function. Haematopoietic ageing refers to the age-related changes affecting a haematopoietic system. Aged blood cells display different functional aberrations depending on their cell type, which might lead to the development of haematologic disorders, including leukaemias, anaemia or declining immunity. In contrast to traditional bulk assays, which are not suitable to dissect cell-to-cell variation, single-cell-level analysis provides unprecedented insight into the dynamics of age-associated changes in blood. In this Review, we summarise recent studies that dissect haematopoietic ageing at the single-cell level. We discuss what cellular changes occur during haematopoietic ageing at the genomic, transcriptomic, epigenomic and metabolomic level, and provide an overview of the benefits of investigating those changes with single-cell precision. We conclude by considering the potential clinical applications of single-cell techniques in geriatric haematology, focusing on the impact on haematopoietic stem cell transplantation in the elderly and infection studies, including recent COVID-19 research.

The Bone Marrow as Sanctuary for Plasma Cells and Memory T-Cells: Implications for Adaptive Immunity and Vaccinology.

The bone marrow (BM) is key to protective immunological memory because it harbors a major fraction of the body's plasma cells, memory CD4+ and memory CD8+ T-cells. Despite its paramount significance for the human immune system, many aspects of how the BM enables decade-long immunity against pathogens are still poorly understood. In this review, we discuss the relationship between BM survival niches and long-lasting humoral immunity, how intrinsic and extrinsic factors define memory cell longevity and show that the BM is also capable of adopting many responsibilities of a secondary lymphoid organ. Additionally, with more and more data on the differentiation and maintenance of memory T-cells and plasma cells upon vaccination in humans being reported, we discuss what factors determine the establishment of long-lasting immunological memory in the BM and what we can learn for vaccination technologies and antigen design. Finally, using these insights, we touch on how this holistic understanding of the BM is necessary for the development of modern and efficient vaccines against the pandemic SARS-CoV-2.