Long non‐coding RNAs (lncRNAs), a large, diverse class of transcribed RNA molecules with a length of more than 200 nucleotides that do not encode proteins, represent important regulators of gene expression that impact a wide range cellular processes. LncRNAs mediate transcriptional regulation or chromatin modification both in cis and in trans, bind to complementary RNA to affect processing, turnover, and localization, and interact with proteins to impact function and localization and form riboprotein complexes.1 While the exact function of the vast majority of the 30 000 estimated lncRNAs present in the human genome remains uninvestigated, there exists ample evidence that lncRNAs play crucial roles in stem cell differentiation and cell fate determination. Examples include the RMST lncRNA, which physically interacts with SOX2 and acts as a transcriptional coregulator to modulate the fate of neural stem cells,2 and LNCRNA‐HIT, which promotes the expression of multiple genes that foster the formation of cartilage in the mouse embryo limb mesenchyme.3 What other examples of stem/progenitor cell‐specific lncRNAs exist, and how do they control stem cell differentiation and cell fate? In the first of our Featured Articles published this month in STEM CELLS Translational Medicine, Chen et al. report on the identification of a new lncRNA highly expressed in adipose‐derived mesenchymal stem cells (ASCs) undergoing differentiation into adipocytes that may aid the development of novel therapeutics for metabolic disorders.4 In a Related Article published recently in STEM CELLS, Tang et al. identified a novel osteogenesis‐associated lncRNA in differentiating bone marrow mesenchymal stem cells (MSCs) that regulates the activation of the bone morphogenetic protein (BMP) signaling pathway by interacting with an RNA binding protein.5

The progressive degeneration of the central nervous system characterizes Alzheimer's disease, the most common form of age‐related dementia. Neuropathological hallmarks include the presence of extracellular beta‐amyloid plaques and neurofibrillary tangles containing a hyperphosphorylated microtubule‐associated protein, inflammation, synaptic and neuronal dysfunction, and neural degeneration.6 Microglia‐mediated neuroinflammation can exacerbate Alzheimer's disease‐related pathologies to drive neuronal injury,7 and studies have also established that microglia express many Alzheimer's disease risk genes.8 Studies such as these highlight microglial targeting and the reduction of neuroinflammation as a potentially efficient treatment approach; can we take advantage of the well‐known immunomodulatory and anti‐inflammatory abilities of MSCs to develop an effective treatment for Alzheimer's disease? Oxidative stress also contributes to the development of Alzheimer's disease by reducing neural proliferation, differentiation, and survival and hence negatively impacting neurogenesis. The increased oxidative stress associated with beta‐amyloid toxicity can induce the inflammation and the subsequent pathological and cognitive abnormalities observed in Alzheimer's disease patients.9 Furthermore, this inhospitable environment can inhibit the proper function of resident or exogenously administered stem/progenitor cells; can we provide said cells with a means to protect themselves to improve outcomes in Alzheimer's disease patients? In the second of our Featured Articles published this month in STEM CELLS Translational Medicine, Losurdo et al. demonstrate that the intranasal administration of extracellular vesicles derived from MSCs dampens pathogenic inflammation and induces neuroprotective effects in a triple transgenic mouse model of Alzheimer's disease.10 In a Related Article published recently in STEM CELLS, Kärkkäinen et al. reported the involvement of a transcription factor associated with the oxidative stress response in the neuronal differentiation of neural progenitor cells (NPCs), the regulation of injury‐induced neurogenesis, and protection against the development of Alzheimer's disease .11

长的非编码RNA（lncRNA）是一大类多样的转录RNA分子，长度超过200个核苷酸，不编码蛋白质，代表了影响广泛细胞过程的重要基因表达调节剂。LncRNA介导顺式和反式的转录调节或染色质修饰，与互补RNA结合以影响加工，周转和定位，并与蛋白质相互作用以影响功能和定位并形成核糖蛋白复合物。1个尽管人类基因组中存在的3万种估计的lncRNA中绝大多数的确切功能尚待研究，但有充分的证据表明lncRNA在干细胞分化和细胞命运确定中起着至关重要的作用。例子包括RMST lncRNA，它与SOX2发生物理相互作用，并作为转录调节剂来调节神经干细胞的命运2和LNCRNA-HIT，后者促进多种基因的表达，这些基因促进小鼠胚胎肢体软骨的形成间充质。3还有其他干/祖细胞特异性lncRNA的例子，它们如何控制干细胞分化和细胞命运？在本月发表于《STEM细胞转化医学》上的第一篇精选文章中，Chen等。关于鉴定在脂肪来源的间充质干细胞（ASC）中高度表达的新lncRNA的报告，该细胞正在分化为脂肪细胞，这可能有助于开发新的代谢紊乱疗法。4 Tang等人最近在STEM CELLS中发表的相关文章中。在分化的骨髓间充质干细胞（MSC）中鉴定了一种新型的成骨相关lncRNA，该mRNA通过与RNA结合蛋白相互作用来调节骨形态发生蛋白（BMP）信号通路的激活。5

中枢神经系统的逐步变性是阿尔茨海默氏病的特征，阿尔茨海默氏病是与年龄有关的痴呆的最常见形式。神经病理学特征包括细胞外β-淀粉样蛋白斑块和含有高磷酸化微管相关蛋白的神经原纤维缠结，炎症，突触和神经元功能障碍以及神经变性。6小胶质细胞介导的神经炎症会加剧阿尔茨海默氏病的相关疾病，从而引发神经元损伤[ 7]。研究还证实，小胶质细胞表达了许多阿尔茨海默氏病风险基因。8诸如此类的研究强调了靶向小胶质细胞和减少神经炎症作为一种潜在有效的治疗方法。我们能否利用MSC众所周知的免疫调节和抗炎能力来开发有效的阿尔茨海默氏病治疗方法？氧化应激还会通过减少神经增殖，分化和存活，从而对神经发生产生负面影响，从而促进阿尔茨海默氏病的发展。与β-淀粉样蛋白毒性相关的氧化应激增加可诱发炎症以及随后在阿尔茨海默氏病患者中观察到的病理和认知异常。9此外，这种恶劣的环境会抑制常驻或外源性干/祖细胞的正常功能。我们可以为所说的细胞提供保护自身以改善阿尔茨海默氏病患者预后的方法吗？在本月发表于《STEM细胞转化医学》上的第二篇精选文章中， Losurdo等人。证明在鼻内施用源自MSC的细胞外囊泡可减轻致病性炎症，并在阿尔茨海默氏病的三重转基因小鼠模型中诱导神经保护作用。10在最近发表于STEM CELLS的相关文章中，Kärkkäinen等。报道了与氧化应激反应相关的转录因子参与神经祖细胞（NPCs）的神经元分化，损伤诱导的神经发生的调控以及对阿尔茨海默氏病的发展的保护作用。11