Haematopoietic stem cells in perisinusoidal niches are protected from ageing.,Nature Cell Biology

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Haematopoietic stem cells in perisinusoidal niches are protected from ageing.
Nature Cell Biology ( IF 17.3 ) Pub Date : 2019-11-04 , DOI: 10.1038/s41556-019-0418-y
Mehmet Saçma ₁ , Johannes Pospiech ₁ , Ruzhica Bogeska ₂ , Walter de Back ₃ , Jan-Philipp Mallm ₄ , Vadim Sakk ₁ , Karin Soller ₁ , Gina Marka ₁ , Angelika Vollmer ₁ , Rebekah Karns ₅ , Nina Cabezas-Wallscheid ₆ , Andreas Trumpp ₂ , Simón Méndez-Ferrer _{7,

8} , Michael D Milsom ₂ , Medhanie A Mulaw ₉ , Hartmut Geiger _{1,

10} , Maria Carolina Florian _{1,

11}

Affiliation

Institute of Molecular Medicine, Stem Cells and Aging, Aging Research Center, Ulm University, Ulm, Germany.
Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH, Deutsches Krebsforschungszentrum, Division of Experimental Hematology, Heidelberg, Germany.
Institute for Medical Informatics and Biometry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Deutsches Krebsforschungszentrum, Division of Chromatin Network, Heidelberg, Germany.
Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH, USA.
Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Hematology, University of Cambridge, Cambridge, United Kingdom.
National Health Service Blood & Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom.
Molecular Oncology Institute of Experimental Cancer Research, Medical Faculty, University of Ulm, Ulm, Germany.
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH, USA.
Center for Regenerative Medicine in Barcelona, Bellvitge Institute for Biomedical Research, Barcelona, Spain.

With ageing, intrinsic haematopoietic stem cell (HSC) activity decreases, resulting in impaired tissue homeostasis, reduced engraftment following transplantation and increased susceptibility to diseases. However, whether ageing also affects the HSC niche, and thereby impairs its capacity to support HSC function, is still widely debated. Here, by using in-vivo long-term label-retention assays we demonstrate that aged label-retaining HSCs, which are, in old mice, the most quiescent HSC subpopulation with the highest regenerative capacity and cellular polarity, reside predominantly in perisinusoidal niches. Furthermore, we demonstrate that sinusoidal niches are uniquely preserved in shape, morphology and number on ageing. Finally, we show that myeloablative chemotherapy can selectively disrupt aged sinusoidal niches in the long term, which is linked to the lack of recovery of endothelial Jag2 at sinusoids. Overall, our data characterize the functional alterations of the aged HSC niche and unveil that perisinusoidal niches are uniquely preserved and thereby protect HSCs from ageing.

中文翻译：

窦周微环境中的造血干细胞受到保护，免于衰老。

随着年龄的增长，内在造血干细胞（HSC）活性降低，导致组织稳态受损、移植后植入减少以及疾病易感性增加。然而，衰老是否也会影响 HSC 生态位，从而损害其支持 HSC 功能的能力，仍存在广泛争议。在这里，通过使用体内长期标记保留测定，我们证明了老化的标记保留HSC，即老年小鼠中最静止的HSC亚群，具有最高的再生能力和细胞极性，主要存在于窦周微环境中。此外，我们还证明，随着年龄的增长，正弦生态位的形状、形态和数量都得到了独特的保存。最后，我们表明，从长远来看，清髓化疗可以选择性地破坏老化的血窦微环境，这与血窦内皮 Jag2 缺乏恢复有关。总体而言，我们的数据描述了老化 HSC 生态位的功能变化，并揭示了窦周生态位得到独特保存，从而保护 HSC 免于衰老。

更新日期：2019-11-04

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