The progressive onset of abnormal movements, psychiatric problems, and cognitive deficits characterize Huntington's disease,¹ an autosomal-dominant neurodegenerative disorder that affects approximately 5 of every 100 000 people in the United States, Europe, and Australia.² A trinucleotide CAG repeat expansion in the Huntingtin (HTT) gene prompts the production of a mutated protein (mHTT) that misfolds and forms clumped, rigid aggregates³ that prompt the degeneration of efferent medium spiny neurons in the striatum (which coordinates multiple aspects of cognition), a decline in striatal volume, and whole-brain atrophy. Cellular and molecular features of inflammation, including alterations to cytokine levels and microglial activation,⁴ have also been reported as features of Huntington's disease; however, inflammation may represent a protective mechanism during early stage disease,⁵ with neuroinflammatory mechanisms only inducing neuronal death during subsequent progression.^{4, 5} Current research aims include the development of stem cell therapies to inhibit disease progression or treat specific pathologies and the generation of animal models of Huntington's disease to accelerate the clinical translation of said therapies. In the first of our Featured Articles published this month in STEM CELLS Translational Medicine, Dahlenburg et al describe the generation and characterization of an immunodeficient mouse model of Huntington's disease and the subsequent development of a humanized strain to define how the human immune system impacts pathogenesis.⁶ In a Related Article published in STEM CELLS, Yoon et al demonstrated how the intracerebral transplantation of clinical-grade neural stem cells (NSCs) in a rat model of Huntington's disease prompted significant improvements in behavioral and pathological deficits by replacing lost cells and inducing endogenous regeneration.⁷

MicroRNAs (or miRNAs) are short noncoding RNAs of 20 to 25 nucleotides in length that constitute a crucial part of the post-transcriptional regulatory machinery that fine-tunes gene expression.⁸ miRNA-mediated regulation impacts crucial physiological processes, such as development, proliferation, differentiation, and apoptosis, and also participates in disease pathogenesis and aging. miRNAs bind to complementary sequences within target mRNAs to silence expression by cleaving mRNA, destabilizing mRNA, or inhibiting mRNA translation. Alongside proteins, lipids, DNA, and other RNA species, miRNAs comprise one of the major cargos carried by extracellular vesicles, a heterogeneous group of lipid bilayer-delimited particles released by most cells for cell-to-cell communication purposes. Our current appreciation of miRNAs now supports their role as crucial regulators of the self-renewal and differentiation of various stem/progenitor cell populations.⁹ Furthermore, recent research has tightly linked the presence of extracellular vesicle-associated miRNAs to the therapeutic output of stem cell therapies in a range of distinct diseases and disorders.^{10, 11} In the second of our Featured Articles published this month in STEM CELLS Translational Medicine, Ragni et al report on the characterization of the extracellular vesicle-derived miRNA profile of human amniotic membrane-derived MSCs in the hope of accelerating their development into a treatment for diseases such as osteoarthritis.¹² In a Related Article published in STEM CELLS, Channakkar et al described how a brain-enriched miRNA enhanced the differentiation of induced pluripotent stem cell (iPSC)-derived NSCs by altering mitochondrial function in a study that the authors hoped would facilitate the design of treatments for aging-associated neurodegenerative diseases.¹³

异常运动、精神问题和认知缺陷的进行性发作是亨廷顿病¹的特征，这是一种常染色体显性神经退行性疾病，在美国、欧洲和澳大利亚每 10 万人中约有 5 人受到影响。²亨廷顿 ( HTT ) 基因中的三核苷酸 CAG 重复扩增促使产生一种突变蛋白 (mHTT)，该蛋白错误折叠并形成聚集的刚性聚集体³促使纹状体中传出的中等棘状神经元退化（协调认知）、纹状体体积减少和全脑萎缩。炎症的细胞和分子特征，包括细胞因子水平的改变和小胶质细胞的激活，⁴也被报道为亨廷顿病的特征；然而，炎症可能代表早期疾病的一种保护机制， ⁵神经炎症机制仅在随后的进展过程中诱导神经元死亡。^{4, 5}目前的研究目标包括开发干细胞疗法以抑制疾病进展或治疗特定病理，以及生成亨廷顿病动物模型以加速所述疗法的临床转化。在我们本月发表在STEM CELLS Translational Medicine上的第一篇专题文章中, Dahlenburg 等人描述了亨廷顿病免疫缺陷小鼠模型的产生和表征，以及随后开发的人源化菌株，以确定人类免疫系统如何影响发病机制。⁶在STEM CELLS上发表的一篇相关文章中，Yoon 等人展示了在亨廷顿病大鼠模型中临床级神经干细胞 (NSC) 的脑内移植如何通过替换丢失的细胞和诱导内源性再生。⁷

MicroRNA（或 miRNA）是长度为 20 到 25 个核苷酸的短非编码 RNA，构成微调基因表达的转录后调控机制的关键部分。⁸miRNA介导的调控影响重要的生理过程，如发育、增殖、分化和凋亡，还参与疾病发病机制和衰老。miRNA 与靶 mRNA 内的互补序列结合，通过切割 mRNA、破坏 mRNA 或抑制 mRNA 翻译来沉默表达。除了蛋白质、脂质、DNA 和其他 RNA 种类外，miRNA 是细胞外囊泡携带的主要货物之一，细胞外囊泡是大多数细胞释放的一组异质的脂质双层分隔颗粒，用于细胞间通讯目的。我们目前对 miRNA 的认识现在支持它们作为各种干/祖细胞群的自我更新和分化的关键调节剂的作用。⁹此外，最近的研究已将细胞外囊泡相关 miRNA 的存在与干细胞疗法在一系列不同疾病和病症中的治疗输出紧密联系起来。^{10, 11}在我们本月发表在STEM CELLS Translational Medicine上的第二篇专题文章中，Ragni 等人报告了人羊膜来源的 MSCs 的细胞外囊泡来源的 miRNA 谱的表征，希望加速它们发展成为一种治疗骨关节炎等疾病。¹²在STEM CELLS上发表的相关文章中, Channakkar 等人在一项研究中描述了富含大脑的 miRNA 如何通过改变线粒体功能来增强诱导多能干细胞 (iPSC) 衍生的 NSC 的分化，作者希望这项研究有助于设计治疗衰老相关的神经退行性疾病。¹³