长非编码RNAMORRBID调节Bim和短寿命的骨髓细胞寿命
Jonathan J Kotzin1,2, Sean P Spencer1,2, Sam J McCright1,2
1Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Nature
|August 16, 2016
概括
一种新发现的长非编码RNA,Morrbid, 控制了关键免疫细胞如中性粒细胞和单细胞的寿命. 这一发现为炎症性疾病提供了潜在的新治疗点.
科学领域:
- 免疫学
- 分子生物学
- 遗传学
背景情况:
- 中性细胞,乙酸细胞和古典单细胞是免疫反应至关重要的短寿命白细胞.
- 精确调节骨髓细胞寿命对于平衡免疫力和炎症至关重要.
- 控制这些短命骨髓细胞寿命的机制尚未完全理解.
研究的目的:
- 确定控制中性粒细胞,乙酸细胞和古典单细胞寿命的调节机制.
- 研究长非编码RNA在骨髓细胞存活中的作用.
- 探索潜在的炎症疾病治疗点.
主要方法:
- 在小鼠中识别和描述一种称为Morrbid的新型长非编码RNA (lncRNA).
- 对Morrbid在调节中性粒细胞,乙酸细胞和古典单细胞生存中的作用的分析.
- 对Morrbid对亲细胞灭绝基因Bcl2l11 (Bim) 促剂的作用机制的研究,包括PRC2复合体丰富和cis调节.
主要成果:
- 在对促生存细胞因子的反应中,Morbid被确定为中性粒细胞,乙酸细胞和古典单细胞生存的关键调节剂.
- 通过促进剂的PRC2丰富,Morrbid通过调节Bcl2l11 (Bim) 转录来控制细胞寿命.
- 在cis中具有致病作用,可控制Bcl2l11转录和快速亡.
结论:
- 在短寿命的骨髓细胞中,Morrbid提供了局部特异性的调节机制,以快速控制细胞亡.
- 在人体中MORRBID的存在和失调,特别是在高氨基酸性综合征中,表明其作为治疗点的潜力.
- 向MORRBID可能为治疗与异常骨髓细胞寿命相关的炎症性疾病提供一种新的策略.
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