The reprogramming of somatic cells to pluripotency/totipotency via the generation of induced pluripotent stem cells (iPSCs) or by somatic cell nuclear transfer (SCNT) generally suffers from low efficiency. One of the significant obstacles encountered during reprogramming is the need to reset the restrictive epigenetic landscape of somatic cells via the removal of those epigenetic modifications preserving chromatin in a closed state and repressing crucial gene expression programs such as those controlling the initiation and maintenance of pluripotency. The epigenetic landscape includes DNA methylation, histone methylation, and histone acetylation, to name but a few of the currently identified epigenetic modifications that influence gene expression programs and cell fate. Previous studies have sought to improve reprogramming efficiency by inhibiting DNA methylation,1 removing repressive histone modifications (such as histone H3 lysine 9 trimethylation) and increasing the levels of transcriptionally permissive modifications (such as histone acetylation).2 Could the alteration of other epigenetic modifications by targeting relevant modifiers also enhance reprogramming efficiency? Furthermore, could epigenetic alterations expand the differentiation capacity of adult stem cells, such as mesenchymal stem cells (MSCs), to improve their therapeutic potential? In our first Featured Article published this month in STEM CELLS , Jiang et al. report that the overexpression of the KDM6A histone lysine demethylase modulates the epigenetic, transcriptomic, and metabolic profiles of murine somatic cells to improve iPSC reprogramming efficiency.3 In a Related Article published recently in STEM CELLS Translational Medicine , Samsonraj et al. described how the exposure of adipose MSCs to a fungal metabolite increased their osteogenic potential in part by reducing the expression of the EZH2 histone methyltransferase.4

Cancer stem cells (CSCs) possess characteristics associated with normal stem cells, including the ability to self‐renew and differentiate into the cell types found in the tumor type in question. As they significantly contribute to tumor progression, metastasis, chemotherapy resistance, and tumor relapse, CSCs represent a promising target for tumor eradication strategies5; however, conventional anti‐tumorigenic approaches generally lack anti‐CSC efficacy and, therefore, many have sought to develop novel CSC‐specific single and combination therapies or identify new druggable targets. Combinations of conventional and targeted anti‐cancer treatments hold great promise, although such approaches require intimate knowledge of the molecular mechanisms controlling the in vivo characteristics of CSCs. Targeting cells of the tumor‐microenvironment that surround CSCs, otherwise known as the CSC niche,6 represents an attractive alternative anti‐CSC strategy that many have sought to exploit. The full characterization of the interactions between CSCs with niche cells, which include cancer‐associated fibroblasts and cells of the immune system, will aid the development of novel the rapeutic interventions that disrupt the cross‐talk between CSC‐niche cells to inhibit tumor growth. In our second Featured Article published this month in STEM CELLS , Tabu et al. demonstrate that glioma stem cell (GSC)‐derived necrotic particles alter the stem cell niche by influencing the activity of M1‐type tumor‐associated macrophages and promote glioma progression.7 In a Related Article published recently in STEM CELLS Translational Medicine , De Angelis et al. undertook a pan‐omic analysis of patient‐derived colorectal cancer CSC cultures and evaluated their responses to conventional therapeutics in the hope of devising novel treatment approaches and decipher resistance pathways.8

通过产生诱导性多能干细胞（iPSC）或通过体细胞核转移（SCNT）将体细胞重编程为多能/全能的方法通常效率低下。重编程过程中遇到的重大障碍之一是需要通过去除那些保留染色质处于封闭状态的表观遗传修饰并抑制关键的基因表达程序（例如那些控制多能性的启动和维持的程序）来重置体细胞的限制性表观遗传学格局。表观遗传学领域包括DNA甲基化，组蛋白甲基化和组蛋白乙酰化，仅举几个目前确定的影响基因表达程序和细胞命运的表观遗传修饰。1删除了抑制性的组蛋白修饰（例如组蛋白H3赖氨酸9三甲基化）并增加了转录允许修饰的水平（例如组蛋白乙酰化）。2通过靶向相关修饰符改变其他表观遗传修饰是否还能提高重编程效率？此外，表观遗传学改变能否扩大成体干细胞（例如间充质干细胞（MSCs））的分化能力，从而提高其治疗潜力？在本月发表于STEM CELLS的第一篇精选文章中，Jiang等人。报告指出，KDM6A组蛋白赖氨酸脱甲基酶的过表达调节鼠体细胞的表观遗传，转录组和代谢特性，以提高iPSC重编程效率。3在最近发表于STEM CELLS Translational Medicine的相关文章中，Samsonraj等。他描述了脂肪间充质干细胞暴露于真菌代谢产物如何部分地通过降低EZH2组蛋白甲基转移酶的表达来增加其成骨潜能。4

癌症干细胞（CSC）具有与正常干细胞相关的特征，包括自我更新和分化为上述肿瘤类型中发现的细胞类型的能力。由于CSCs显着促进肿瘤进展，转移，化疗耐药性和肿瘤复发，因此代表了肿瘤根除策略的有希望的目标5; 然而，传统的抗肿瘤发生方法通常缺乏抗CSC功效，因此，许多人都在寻求开发新的CSC特异性单一疗法和联合疗法或确定新的可治疗靶标。尽管这类方法需要对控制CSCs体内特征的分子机制有深入的了解，但常规和靶向抗癌治疗的结合还是很有前途的。靶向CSC周围的肿瘤微环境的细胞，也称为CSC生态位，6代表了许多人试图利用的有吸引力的反CSC替代策略。CSC与小生境细胞之间相互作用的完整表征，包括癌症相关的成纤维细胞和免疫系统细胞，将有助于开发新的治疗方法，以破坏CSC小生境细胞之间的串扰，从而抑制肿瘤的生长。在本月发表于STEM CELLS的第二篇精选文章中，Tabu等人。证明神经胶质瘤干细胞（GSC）坏死颗粒通过影响M1型肿瘤相关巨噬细胞的活性并促进神经胶质瘤的进展而改变了干细胞的生态位。7在最近发表在《STEM CELLS转化医学》上的相关文章中，De Angelis等。对源自患者的大肠癌CSC培养物进行了全基因组分析，并评估了它们对常规疗法的反应，以期希望设计出新颖的治疗方法和破译耐药性途径。8