DNA methylation occurs through the transference of a methyl group from the S‐adenosyl‐L‐methionine cosubstrate to the 5‐carbon of the cytosine ring to generate 5‐methylcytosine. This epigenetic modification arises almost exclusively at CpG dinucleotides, in which a cytosine nucleotide is located next to a guanidine nucleotide. The DNA methyltransferase (DNMT) family of enzymes facilitates the transferal of methyl groups, with DNMT1 responsible for the maintenance of established patterns of DNA methylation1 and DNMT3A and 3B responsible for the establishment of de novo DNA methylation patterns.2 DNA demethylation can occur passively, through the absence of functional DNA methylation maintenance machinery, or actively, in a complex process involving the ten‐eleven translocation (TET) family of 5‐methylcytosine hydroxylases and the base excision repair machinery. Elevated levels of DNA methylation at clusters of CpG dinucleotides (known as CpG “islands”) at regulatory regions of genes generally leads to transcriptional inhibition, and vice versa. As DNA methylation patterns, combined with the influence of other epigenetic control mechanisms such as histone post‐translational modifications, dictate the gene expression profiles of a given cell, they play a crucial regulatory role in stem cell function and lineage specification.3 In the first of our Featured Articles published this month in STEM CELLS, Cieslar‐Pobuda et al. report a novel link between the DNMT3B DNA methyltransferase, metabolic flux, and the self‐renewal and differentiation of human embryonic stem cells (ESCs).4 In a Related Article published recently in STEM CELLS Translational Medicine, Kenter et al. generated and characterized human induced pluripotent stem cells (iPSCs) from cystic and healthy control renal epithelial cells for the in vitro modeling of kidney development and cystogenesis, and highlighted the existence of a kidney‐specific DNA methylation‐based epigenetic memory of origin.5

Mammalian target of rapamycin (mTOR), a member of the phosphatidylinositol 3‐kinase‐related kinase family of protein kinases, regulates a range of cellular processes, including cell growth, proliferation, and survival, protein synthesis, and autophagy.6 As mTOR and its associated proteins also play central roles in nutrient sensing and maintaining cellular and metabolic homeostasis,7 the mTOR pathway represents a central regulator of mammalian metabolism and physiology. Of note, the proper function of the liver, muscle, adipose tissue, and brain requires the tight control of mTOR signaling, and pathway dysregulation can induce early‐aging hallmarks and the development of diseases such as diabetes, obesity, and cancer. Interestingly, ongoing research has also underscored the general importance of the mTOR signaling pathway in the regulation of the growth, proliferation, and differentiation of various types of stem and progenitor cells.8 For example, studies have described a requirement for mTOR in the maintenance and differentiation of neural stem cells and brain development, the function of hematopoietic stem cells, the quiescence of hair follicle stem cells, the differentiation of mesenchymal stem cells (MSCs), and the survival of ESCs. In the second of our Featured Articles published this month in STEM CELLS, Liu et al. demonstrate that the mTOR signaling pathway plays contrasting regulatory roles during the commitment/proliferation and maturation phases of the erythropoiesis of human umbilical cord blood‐derived CD34‐positive cells.9 In a Related Article published recently in STEM CELLS Translational Medicine, Liu et al. highlighted the importance of the mTOR signaling pathway to the metabolic reconfiguration observed during the polarization of human MSCs into an immunosuppressive phenotype.10

DNA甲基化是通过将甲基从S-腺苷-L-蛋氨酸的共底物转移到胞嘧啶环的5-碳上而产生的5-甲基胞嘧啶而发生的。这种表观遗传修饰几乎仅在CpG二核苷酸处出现，其中胞嘧啶核苷酸位于胍核苷酸旁边。DNA甲基转移酶（DNMT）酶家族促进甲基的转移，其中DNMT1负责维持DNA甲基化1的既定模式，而DNMT3A和3B负责从头建立DNA甲基化模式。2DNA脱甲基可以通过缺少功能性的DNA甲基化维持机制而被动发生，也可以在涉及5-甲基胞嘧啶羟化酶的十一十一易位（TET）家族和碱基切除修复机制的复杂过程中主动发生。基因调节区域的CpG二核苷酸簇（称为CpG“岛”）上的DNA甲基化水平升高通常会导致转录抑制，反之亦然。由于DNA甲基化模式与其他表观遗传控制机制（如组蛋白翻译后修饰）的影响共同决定了给定细胞的基因表达谱，因此它们在干细胞功能和谱系规范中起着至关重要的调节作用。3在本月发表的第一篇精选文章中，干细胞，Cieslar-Pobuda等。报告了DNMT3B DNA甲基转移酶，代谢通量与人类胚胎干细胞（ESC）的自我更新和分化之间的新颖联系。4在最近发表于《STEM CELLS转化医学》（肯特等人）的相关文章中。从囊性和健康对照肾上皮细胞中产生并鉴定了人类诱导的多能干细胞（iPSC），用于体外建模肾脏发育和囊肿形成，并强调了存在基于肾脏特异性DNA甲基化的表观遗传记忆。5

雷帕霉素（mTOR）的哺乳动物靶标是磷脂酰肌醇3激酶相关蛋白激酶家族的成员，它调节一系列细胞过程，包括细胞生长，增殖和存活，蛋白质合成和自噬。6由于mTOR及其相关蛋白在营养物传感以及维持细胞和代谢稳态方面也起着核心作用，7mTOR途径代表哺乳动物代谢和生理的中央调节剂。值得注意的是，肝脏，肌肉，脂肪组织和大脑的正常功能需要严格控制mTOR信号传导，并且通路失调可以诱发早期衰老的标志和诸如糖尿病，肥胖症和癌症等疾病的发展。有趣的是，正在进行的研究还强调了mTOR信号通路在调节各种类型干细胞和祖细胞的生长，增殖和分化中的普遍重要性。8例如，研究描述了mTOR在神经干细胞的维持和分化以及大脑发育，造血干细胞的功能，毛囊干细胞的静止，间充质干细胞（MSC）的分化， ESC的存活率。在本月发表于STEM CELLS的第二篇精选文章中，Liu等人。证明了mTOR信号通路在人脐带血CD34阳性细胞的促红细胞生成的定型/增殖和成熟阶段起着相反的调节作用。9在最近发表在《STEM CELLS转化医学》上的相关文章中，Liu等。强调了mTOR信号通路对人类MSC分化为免疫抑制表型期间观察到的代谢重构的重要性。10