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核糖体水平选择性调节人类血液形成中的转化和血统结合

Rajiv K Khajuria¹, Mathias Munschauer², Jacob C Ulirsch³

¹Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Berlin-Brandenburg School for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin 13353, Germany.

|March 20, 2018

概括

钻石黑人贫血 (DBA) 显示,减少的核糖体水平,而不是组成, 损害了血细胞的形成. 这一发现突显了核糖体水平作为血造干细胞和前代细胞 (HSPC) 中正常和受损的红细胞系承诺的关键调节者.

科学领域:

血液学
分子生物学
遗传学

背景情况:

血细胞形成传统上遵循一个等级差异化模式.
最近的研究表明,在造血干细胞和原生细胞 (HSPC) 中早些时候的血统承诺.
这些精细模型的监管和疾病相关性尚不清楚.

研究的目的:

在正常和疾病状态下调查血统承诺编程的机制基础.
探索核糖体蛋白突变在钻石黑贫血 (DBA) 中的作用及其对红细胞系的影响.
了解核糖体水平的变化如何影响细胞分化.

主要方法:

研究了一组患有Diamond-Blackfan贫血症 (DBA) 的患者,这是一种遗传性血液疾病.
在血造干细胞和前代细胞 (HSPC) 中分析了核糖体水平和组成.
研究了改变核糖体水平对转录翻译和谱系承诺的影响.

主要成果:

DBA的特点是有限的可用核糖体池,核糖体组成不变.
核糖体水平的全球降低不成比例地影响特定转录的翻译.
在HSPC中选择转录的减少被证明是阻碍了红状腺血统的结合.

结论:

核糖体水平,而不是组成,在细胞分化中起着关键的调节作用.
由于核糖体可用性有限,DBA中的红细胞系承诺受损与特定转录的翻译减少有关.
这项研究揭示了血液细胞形成和疾病发病的新型调节机制.

关键词:

钻石黑人贫血症在 GATA 红色形成遗传学血液形成血统承诺核糖体翻译

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