研究人员发现，在妊娠期间和出血后，造血干细胞（HSC）和红细胞生成通过去抑制逆转录转座子（包括内源性逆转录病毒和LINE元素）而被激活。
逆转录转座子的转录激活了先天免疫传感器环鸟苷酸-腺苷酸合成酶（cGAS）和干扰素（IFN）基因刺激因子（STING），从而诱导HSC中IFN和IFN调控基因的表达，增加HSC的分裂和红细胞生成。
在非妊娠小鼠中，逆转录酶抑制剂或cGAS或STING缺失对造血的影响很小或没有影响，但在妊娠小鼠中会耗竭HSC和红细胞前体，降低红细胞计数。
逆转录转座子和IFN调控基因在小鼠HSC经历多次出血和人类HSC在妊娠期间也被诱导。逆转录酶抑制剂的使用与妊娠期人群的贫血相关，但在非妊娠人群中没有这种现象，这表明这些机制在小鼠和人类之间具有保守性。
附：英文原文
Title: Retrotransposons are co-opted to activate hematopoietic stem cells and erythropoiesis
Author: Julia Phan, Brandon Chen, Zhiyu Zhao, Gabriele Allies, Antonella Iannaccone, Animesh Paul, Feyza Cansiz, Alberto Spina, Anna-Sophia Leven, Alexandra Gellhaus, Dirk Schadendorf, Rainer Kimmig, Marcel Mettlen, Alpaslan Tasdogan, Sean J. Morrison
Issue&Volume: 2024-10-24
Abstract: Hematopoietic stem cells (HSCs) and erythropoiesis are activated during pregnancy and after bleeding by the derepression of retrotransposons, including endogenous retroviruses and LINE elements. Retrotransposon transcription activates the innate immune sensors cyclic GMP-AMP synthase (cGAS) and stimulator of interferon (IFN) genes (STING), which induce IFN and IFN-regulated genes in HSCs, increasing HSC division and erythropoiesis. Inhibition of reverse transcriptase or deficiency for cGAS or STING had little or no effect on hematopoiesis in non-pregnant mice but depleted HSCs and erythroid progenitors in pregnant mice, reducing red blood cell counts. Retrotransposons and IFN regulated genes were also induced in mouse HSCs after serial bleeding and in human HSCs during pregnancy. Reverse transcriptase inhibitor use was associated with anemia in pregnant, but not non-pregnant, people suggesting conservation of these mechanisms from mice to humans.
DOI: ado6836
Source: https://www.science.org/doi/10.1126/science.ado6836