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逆转录转座子被募集来激活造血干细胞和红细胞生成。

Retrotransposons are co-opted to activate hematopoietic stem cells and erythropoiesis.

机构信息

Children's Research Institute and the Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Department of Dermatology, University Hospital Essen & German Cancer Consortium, Essen, & National Center for Tumor Diseases (NCT-West), Campus Essen & Research Alliance Ruhr, Research Center One Health, University Duisburg-Essen, Campus Essen, Essen, Germany.

出版信息

Science. 2024 Nov 8;386(6722):eado6836. doi: 10.1126/science.ado6836.

DOI:10.1126/science.ado6836
PMID:39446896
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11709122/
Abstract

Hematopoietic stem cells (HSCs) and erythropoiesis are activated during pregnancy and after bleeding by the derepression of retrotransposons, including endogenous retroviruses and long interspersed nuclear elements. Retrotransposon transcription activates the innate immune sensors cyclic guanosine 3',5'-monophosphate-adenosine 5'-monophosphate 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 nonpregnant 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 in nonpregnant people, suggesting conservation of these mechanisms from mice to humans.

摘要

造血干细胞 (HSCs) 和红细胞生成在怀孕期间和出血后通过逆转录转座子的去抑制被激活，包括内源性逆转录病毒和长散布核元件。逆转录转座子转录激活先天免疫传感器环鸟苷酸 3'，5'-单磷酸-腺苷 5'-单磷酸合酶 (cGAS) 和干扰素 (IFN) 基因刺激物 (STING)，诱导 HSCs 中的 IFN 和 IFN 调节基因，增加 HSC 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 的缺乏对造血几乎没有影响，但在妊娠小鼠中耗尽了 HSCs 和红系祖细胞，导致红细胞计数减少。在小鼠 HSCs 中，逆转录转座子和 IFN 调节基因也在多次出血后被诱导，在人类 HSCs 中，在怀孕期间也被诱导。逆转录酶抑制剂的使用与妊娠妇女的贫血有关，但与非妊娠妇女无关，提示这些机制从小鼠到人类是保守的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d169/11709122/5960b02477f3/nihms-2042983-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d169/11709122/5623fa562958/nihms-2042983-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d169/11709122/3d4ffc439abb/nihms-2042983-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d169/11709122/81b04ef1087e/nihms-2042983-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d169/11709122/53be22e9df06/nihms-2042983-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d169/11709122/a2b1f8f0ddc5/nihms-2042983-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d169/11709122/5960b02477f3/nihms-2042983-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d169/11709122/5623fa562958/nihms-2042983-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d169/11709122/3d4ffc439abb/nihms-2042983-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d169/11709122/81b04ef1087e/nihms-2042983-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d169/11709122/53be22e9df06/nihms-2042983-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d169/11709122/a2b1f8f0ddc5/nihms-2042983-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d169/11709122/5960b02477f3/nihms-2042983-f0007.jpg

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