内源性逆转录元件的调控
中文名称
通路描述
PIWI 相互作用 RNA（piRNAs）是 24-31 个核苷酸短 RNA，通过“乒乓”机制（涉及链杂交和切割）从更长 RNA 切割并扩增产生（综述：Sun 等，2022）。piRNAs 被加载到 PIWI 蛋白（PIWIL1, PIWIL2, PIWIL4）上，并通过 piRNA 与新生和成熟转录本碱基配对，引导 PIWI:piRNA 复合物分别启动转录后和转录后转录抑制（综述：Czech 等，2018, Onishi 等，2021, Wang 等，2023）。在老鼠中，piRNAs 的来源包括转座子 RNA、长非编码 RNA、外显子转录本和基因组未注释区域的 RNA（Aravin 等，2007, 2008）。在老鼠发育过程中观察到两种 piRNA 种群：前期 pachytene piRNAs 和后期 pachytene piRNAs（Aravin 等，2008, Gan 等，2011）。前期 pachytene piRNAs 在胎儿期存在于 prospermatogonial 细胞中，在出生后存在于精原细胞中。后期 pachytene piRNAs 存在于更成熟的后期减数分裂精母细胞和精母细胞中。来自逆转录元件的 piRNAs 约占前期 pachytene piRNAs 的一半（Aravin 等，2008）或更少（Gan 等，2011），且从前期 pachytene 到 pachytene 的比例急剧下降（Gan 等，2011）。在老鼠中，PIWIL2（MILI, Piwil2 基因）在原始生殖细胞达到生殖嵴时首次检测到，表达持续至成年期的减数分裂。PIWIL4（MIWI2, PIWIl4 基因）在新生小鼠的生殖细胞中存在于去甲基化 DNA shortly before 和 after 出生。PIWIL1（MIWI, PIWIL1 基因）在出生后的减数分裂后期存在（Aravin 等，2008）。PIWIL4 和 PIWIL2 参与小鼠生殖细胞中基因组重甲基化及转座元件的相应抑制（Carmell 等，2007, Aravin 等，2008, Kuramochi-Miyagawa 等，2008, Zoch 等，2020）。在老鼠中，与 PIWIL4 结合的 piRNAs 结合新生转座子转录本，并通过 SPOCD1 和 C19ORF84 连接到去甲基化 DNA 甲基化机器，将 DNA 甲基化导向转座子（Zoch 等，2020, 2024）。SPOCD1 突变与男性不育相关（Zoch 等，2024）。
英文描述
Developmental Lineage of Mammary Gland Myoepithelial Cells Most postnatal mammary gland development originates from unipotent lineage-committed progenitors (luminal progenitor cells and myoepithelial progenitor cells), which are located in the basal epithelium (reviewed in Inman et al. 2015, Edwards and Brennan 2021).Myoepithelial cells, which originate from myoepithelial progenitors, are located between luminal cells that line the mammary ducts and alveoli, and the basement membrane (reviewed in Stingl et al. 2005). Myoepithelial cells form a continuous sheath around the ducts but are sparser around the alveoli, where their cytoplasmic processes create a basket-like structure that allows some luminal cells to come in contact with the basement membrane (reviewed in Stingl et al. 2005). Myoepithelial cells are spindle shaped and are able to contract in response to oxytocin, which is necessary for milk secretion (lactation) (reviewed in Stingl et al. 2005, and Watson and Khaled 2020).Upon ablation of the luminal epithelial cells in the adult mouse mammary gland, unipotent myoepithelial progenitor cells can convert into unipotent luminal progenitors to repopulate the luminal lineage (Centonze et al. 2020, reviewed in Edwards and Brennan 2021). In mouse mammary glands, tumor necrosis factor (TNF), secreted by luminal cells, restricts multipotency of myoepithelial progenitors under normal physiological conditions (Centonze et al. 2020). After ablation of luminal cells, Notch, Wnt and EGFR signaling pathways are activated in myoepithelial progenitor cells, promoting regeneration-induced multipotency of myoepithelial progenitors (Centonze et al. 2020, reviewed in Edwards and Brennan 2021). In human mammary organoids, high intensity EGFR signaling promotes myoepithelial cell fate (Pasic et al. 2011, Mukhopadyay et al. 2013). FGF2 and FGF7 are not necessary for the differentiation of myoepithelial cells in human mammary organoids, but they are needed for the establishment of proper architecture of mammary ducts (Pasic et al. 2011).
所含基因
18 个基因