小柯机器人

西班牙巴塞罗那理工学院Salvador Aznar Benitah、Alexandra Avgustinova等研究人员合作发现，抑制内源性逆转录病毒可防止抗病毒免疫反应，并且是乳腺发育所必需的。相关论文于2021年5月18日在线发表于国际学术期刊《细胞—干细胞》。

研究人员证明，在乳腺上皮中组蛋白H3第9位赖氨酸（H3K9）甲基转移酶G9a的丢失导致从头染色质打开、乳腺导管树异常形成、干细胞潜能的受损、导管内极性破坏和组织功能丧失。G9a丢失会抑制长末端重复（LTR）逆转录病毒序列（主要是ERVK家族）。转录激活的内源性逆转录病毒会生成双链DNA（dsDNA），从而触发抗病毒先天免疫反应，并在G9a敲除（G9acKO）乳腺上皮细胞中敲除胞质dsDNA传感器Aim2，并挽救乳腺导管的侵袭。

乳腺干细胞能够移植到免疫功能低下或G9acKO条件的宿主中，这表明G9acKO乳腺形态缺陷部分依赖于宿主乳腺脂肪垫的炎症环境。因此，改变逆转录病毒元件的染色质可及性通过细胞自主和非自主机制破坏了乳腺发育和干细胞活性。

附：英文原文

Title: Repression of endogenous retroviruses prevents antiviral immune response and is required for mammary gland development

Author: Alexandra Avgustinova, Carmelo Laudanna, Mónica Pascual-García, Quirze Rovira, Magdolna Djurec, Andres Castellanos, Uxue Urdiroz-Urricelqui, Domenica Marchese, Neus Prats, Alexandra Van Keymeulen, Holger Heyn, Juan M. Vaquerizas, Salvador Aznar Benitah

Issue&Volume: 2021-05-18

Abstract: The role of heterochromatin in cell fate specification during development is unclear.We demonstrate that loss of the lysine 9 of histone H3 (H3K9) methyltransferase G9ain the mammary epithelium results in de novo chromatin opening, aberrant formation of the mammary ductal tree, impaired stem cellpotential, disrupted intraductal polarity, and loss of tissue function. G9a loss derepresseslong terminal repeat (LTR) retroviral sequences (predominantly the ERVK family). Transcriptionallyactivated endogenous retroviruses generate double-stranded DNA (dsDNA) that triggersan antiviral innate immune response, and knockdown of the cytosolic dsDNA sensor Aim2 in G9a knockout (G9acKO) mammary epithelium rescues mammary ductal invasion. Mammarystem cell transplantation into immunocompromised or G9acKO-conditioned hosts showspartial dependence of the G9acKO mammary morphological defects on the inflammatorymilieu of the host mammary fat pad. Thus, altering the chromatin accessibility ofretroviral elements disrupts mammary gland development and stem cell activity throughboth cell-autonomous and non-autonomous mechanisms.

DOI: 10.1016/j.stem.2021.04.030

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00206-X

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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