Adult skull bone marrow is an expanding and resilient haematopoietic reservoir

• 成果类型: Article
• 署名作者: Koh, Bong Ihn; Mohanakrishnan, Vishal; Jeong, Hyun-Woo; Park, Hongryeol; Kruse, Kai; Choi, Young Jun; Nieminen-Kelhae, Melina; Kumar, Rahul; Pereira, Raquel S.; Adams, Susanne; Lee, Hyuek Jong; Bixel, M. Gabriele; Vajkoczy, Peter; Krause, Daniela S.; Adams, Ralf H.
• 署名单位: Max Planck Society; Max Planck Society; Max Planck Society; University of Ulsan; Asan Medical Center; University of Ulsan; Asan Medical Center; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Free University of Berlin; Humboldt University of Berlin; Johannes Gutenberg University of Mainz; Goethe University Frankfurt; Institute for Basic Science - Korea (IBS)
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6667
• DOI: 10.1038/s41586-024-08163-9
• 发表日期: 2024-12-05
• 关键词: cell metabolism; stem; vegf; mechanisms; reveals; disease; HEALTH; niches; mice; AGE

摘要

The bone marrow microenvironment is a critical regulator of haematopoietic stem cell self-renewal and fate1. Although it is appreciated that ageing, chronic inflammation and other insults compromise bone marrow function and thereby negatively affect haematopoiesis2, it is not known whether different bone compartments exhibit distinct microenvironmental properties and functional resilience. Here we use imaging, pharmacological approaches and mouse genetics to uncover specialized properties of bone marrow in adult and ageing skull. Specifically, we show that the skull bone marrow undergoes lifelong expansion involving vascular growth, which results in an increasing contribution to total haematopoietic output. Furthermore, skull is largely protected against major hallmarks of ageing, including upregulation of pro-inflammatory cytokines, adipogenesis and loss of vascular integrity. Conspicuous rapid and dynamic changes to the skull vasculature and bone marrow are induced by physiological alterations, namely pregnancy, but also pathological challenges, such as stroke and experimental chronic myeloid leukaemia. These responses are highly distinct from femur, the most extensively studied bone marrow compartment. We propose that skull harbours a protected and dynamically expanding bone marrow microenvironment, which is relevant for experimental studies and, potentially, for clinical treatments in humans. Skull bone marrow expands during adult life, exhibits lifelong vascular growth and increases its haematopoietic potential during ageing.