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Characterization of naked mole-rat hematopoiesis reveals unique stem and progenitor cell patterns and neotenic traits
The EMBO Journal ( IF 9.4 ) Pub Date : 2022-06-13 , DOI: 10.15252/embj.2021109694
Stephan Emmrich 1 , Alexandre Trapp 1 , Frances Tolibzoda Zakusilo 1 , Maggie E Straight 1 , Albert K Ying 2 , Alexander Tyshkovskiy 2 , Marco Mariotti 2 , Spencer Gray 1 , Zhihui Zhang 1 , Michael G Drage 3 , Masaki Takasugi 1 , Jan-Henning Klusmann 4 , Vadim N Gladyshev 2 , Andrei Seluanov 1 , Vera Gorbunova 1
Affiliation  

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.

中文翻译:

裸鼹鼠造血的表征揭示了独特的干细胞和祖细胞模式以及幼态持续特征

裸鼹鼠(NMR)是最长寿的啮齿动物,但它们的干细胞特征仍然是个谜。在这里,我们全面绘制了核磁共振造血图谱,并确定了可能有助于长寿的独特特征。成人 NMR 在脾脏和骨髓中形成红细胞,其中包括粒细胞生成的骨髓偏向以及 B 淋巴细胞生成的减少。值得注意的是,年轻时的血液和骨髓单细胞转录组和细胞组成基本上维持到至少中年。与灵长类动物类似,原始干细胞和祖细胞 (HSPC) 区室由 CD34 和 THY1 标记。微管蛋白具有干细胞极性,但 CDC42 不具有干细胞极性,并且直到 12 岁时才会丢失。HSPC 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相一致。静止干细胞库比小鼠高,造血细胞的细胞周期延长。通过表征 NMR 造血景观,我们确定了恢复表型,例如静态 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幼态持续特征。
更新日期:2022-06-13
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