Cell Stem Cell:SON是影響造血干細胞命運的重要m6A靶點

2023年12月7日,來自美國紀念斯隆-凱特琳癌癥中心Michael G. Kharas研究組在學術期刊《細胞-干細胞》發表了標題為“SON is an essential m6A target for hematopoietic stem cell fate.”的研究成果,發現SON是影響造血干細胞命運的重要m6A靶點。


據悉,干細胞通過對稱和非對稱分裂來調節自我更新和分化命運決定。RNA m6A甲基化通過未知機制控制造血干細胞對稱分裂和炎癥。

研究人員證明核斑點蛋白SON是小鼠造血干細胞自我更新、對稱分裂和炎癥控制所必需的m6A靶點。對m6A的全局分析發現,在造血干細胞分裂過程中,Son mRNA的m6A甲基化增加。當m6A缺失時,Son mRNA增加,但其蛋白會耗竭。重新表達SON可挽救造血干細胞對稱分裂和移植缺陷。相反,Son缺失則會導致造血干細胞功能喪失,而過表達SON通過增加靜止期來改善小鼠和人造血干細胞的移植潛力。




  • ?DART-seq identified SON as an m6A target critical for HSC commitment
  • ?SON rescues m6A HSC defect and is asymmetrically segregated during HSC division
  • ?SON enhances mouse and human HSC function
  • ?The m6A-SON-CCL5 axis controls HSC inflammation and fate


Stem cells regulate their self-renewal and differentiation fate outcomes through both symmetric and asymmetric divisions. m6A RNA methylation controls symmetric commitment and inflammation of hematopoietic stem cells (HSCs) through unknown mechanisms. Here, we demonstrate that the nuclear speckle protein SON is an essential m6A target required for murine HSC self-renewal, symmetric commitment, and inflammation control. Global profiling of m6A identified that m6A mRNA methylation of?Son?increases during HSC commitment. Upon m6A depletion,?Son?mRNA increases, but its protein is depleted. Reintroduction of SON rescues defects in HSC symmetric commitment divisions and engraftment. Conversely,?Son?deletion results in a loss of HSC fitness, while overexpression of SON improves mouse and human HSC engraftment potential by increasing quiescence. Mechanistically, we found that SON rescues MYC and suppresses the METTL3-HSC inflammatory gene expression program, including CCL5, through transcriptional regulation. Thus, our findings define a m6A-SON-CCL5 axis that controls inflammation and HSC fate.



Hanzhi Luo, Mariela Cortés-López, Cyrus L. Tam et al, SON is an essential m6A target for hematopoietic stem cell fate.DOI: 10.1016/j.stem.2023.11.006,Cell Stem Cell:最新IF:25.269




:?: :razz: :sad: :evil: :!: :smile: :oops: :grin: :eek: :shock: :???: :cool: :lol: :mad: :twisted: :roll: :wink: :idea: :arrow: :neutral: :cry: :mrgreen: