Department of Biology, University of Rochester, Rochester, NY, USA.
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
EMBO J. 2022 Aug 1;41(15):e109694. doi: 10.15252/embj.2021109694. Epub 2022 Jun 13.
Naked mole rats (NMRs) are the longest-lived rodents yet their stem cell characteristics remain enigmatic. Here, we comprehensively mapped the NMR hematopoietic landscape and identified unique features likely contributing to longevity. Adult NMRs form red blood cells in spleen and marrow, which comprise a myeloid bias toward granulopoiesis together with decreased B-lymphopoiesis. Remarkably, youthful blood and marrow single-cell transcriptomes and cell compositions are largely maintained until at least middle age. Similar to primates, the primitive stem and progenitor cell (HSPC) compartment is marked by CD34 and THY1. Stem cell polarity is seen for Tubulin but not CDC42, and is not lost until 12 years of age. HSPC respiration rates are as low as in purified human stem cells, in concert with a strong expression signature for fatty acid metabolism. The pool of quiescent stem cells is higher than in mice, and the cell cycle of hematopoietic cells is prolonged. By characterizing the NMR hematopoietic landscape, we identified resilience phenotypes such as an increased quiescent HSPC compartment, absence of age-related decline, and neotenic traits likely geared toward longevity.
裸鼹鼠（NMRs）是寿命最长的啮齿动物，但它们的干细胞特性仍然是个谜。在这里，我们全面绘制了 NMR 造血景观图，并鉴定了可能有助于长寿的独特特征。成年 NMR 在脾脏和骨髓中形成红细胞，这包括向粒细胞生成的偏倚，同时减少 B 淋巴细胞生成。值得注意的是，年轻的血液和骨髓单细胞转录组和细胞组成在至少中年之前基本保持不变。与灵长类动物相似，原始的干细胞和祖细胞（HSPC）区室由 CD34 和 THY1 标记。Tubulin 显示出干细胞极性，但 CDC42 没有，并且直到 12 岁才丧失。HSPC 的呼吸速率与纯化的人类干细胞一样低，与脂肪酸代谢的强烈表达特征一致。静止的干细胞池比在小鼠中更高，造血细胞的细胞周期延长。通过对 NMR 造血景观进行表征，我们鉴定了具有弹性的表型，如静止的 HSPC 区室增加、不存在与年龄相关的衰退以及可能有助于长寿的新态特征。
