Mouse epiblast stem cells (EpiSCs) are derived from the postimplantation epiblast of the developing embryo and resemble human embryonic stem cells (ESCs) in terms of morphology, the pathways employed for self‐renewal, and other related molecular characteristics.^{1, 2} Mouse EpiSCs exist in a “primed” pluripotent state and are epigenetically distinct from mouse ESCs, which themselves exist in a “naïve” pluripotent state (or the ground state).³ Detailed analyses of the conversion of EpiSCs into the naïve pluripotent state have fostered an in‐depth understanding of the intricate reprogramming mechanisms involved, research which has supported the successful derivation of human naïve ESCs. Mouse EpiSCs maintain their self‐renewal capacity via signaling through the Activin/Nodal and fibroblast growth factor (FGF)/ERK pathways; furthermore, Wnt signaling pathway inhibition can favor EpiSC growth and pluripotency.⁴ EpiSCs also possess the potential to differentiate into cells of the three germ‐layers, can form teratomas, and undergo random X‐chromosome inactivation like the postimplantation epiblast.³ Overall, EpiSCs represent a valuable tool for the understanding of critical developmental mechanisms. In the first of our Featured Articles published this month in STEM CELLS Translational Medicine, Gao et al employ a massive mutagenesis protocol in their newly developed mouse haploid EpiSCs to identify candidate genes that modulate the reprogramming of EpiSCs to naïve pluripotency.⁵ In a Related Article published recently in STEM CELLS, Sudheer et al highlighted the important role of FGF signaling in the differentiation of mouse ESCs through an EpiSC‐like state into distinct presomitic mesodermal cell types in a study that may permit a deeper understanding of musculoskeletal disorders that arise during early development.⁶

Bacterial and viral pneumonia and sepsis represent the most common causes of acute respiratory distress syndrome (ARDS), which remains a leading cause of disability and death in critically ill patients.⁷ Excessive pulmonary inflammation mediated by the reaction of resident macrophages to infection represents the main characteristic of ARDS pathophysiology.⁸ Although the search for effective treatments for ARDS has been ongoing for many years, this area has recently come under sharp focus due to the worldwide impact of coronavirus disease 2019 (COVID‐19), a pneumonia‐like disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2).^{9, 10} Severe COVID‐19 patients present with hyper‐inflammation, an overactive immune response that triggers a “cytokine storm,” and a prothrombotic state that can progress to ARDS development, with reported patient mortality reaching over 50%.¹¹ Mesenchymal stem cell (MSC) therapy represents a potentially effective treatment option for ARDS, with ongoing trials now evaluating this approach in severe COVID‐19 patients and related research attempting to delineate the molecular mechanisms behind the therapeutic effect of MSCs in the bacterially‐induced form of the disease. In the second of our Featured Articles published this month in STEM CELLS Translational Medicine, Lanzoni et al report on the encouraging findings of a double‐blind, randomized, controlled, early phase clinical trial of umbilical cord‐derived MSC treatment in patients with COVID‐19‐related ARDS.¹² In a Related Article published recently in STEM CELLS, Jackson et al demonstrated that mitochondrial transfer to macrophages represents a crucial mechanism by which MSCs mediate their therapeutic capacity in bacterially‐induced ARDS.¹³

小鼠外胚层干细胞 (EpiSC) 源自发育中胚胎的植入后外胚层，在形态、自我更新途径和其他相关分子特征方面与人类胚胎干细胞 (ESC) 相似。^{1, 2}小鼠 EpiSC 以“启动”多能状态存在，并且在表观遗传上与小鼠 ESC 不同，后者本身以“初始”多能状态（或基态）存在。³对 EpiSC 向幼稚多能状态转化的详细分析促进了对所涉及的复杂重编程机制的深入了解，这些研究支持了人类幼稚 ESC 的成功衍生。小鼠 EpiSC 通过 Activin/Nodal 和成纤维细胞生长因子 (FGF)/ERK 通路的信号传导来维持自我更新能力；此外，Wnt 信号通路抑制有利于 EpiSC 的生长和多能性。⁴ EpiSC 还具有分化为三个胚层细胞的潜力，可以形成畸胎瘤，并像植入后外胚层一样经历随机 X 染色体失活。³总体而言，EpiSC 是理解关键发育机制的宝贵工具。在我们本月在STEM CELLS Translational Medicine上发表的第一篇专题文章中，Gao 等人在他们新开发的小鼠单倍体 EpiSC 中采用了大规模诱变方案，以确定调节 EpiSC 重编程为幼稚多能性的候选基因。⁵在STEM CELLS最近发表的一篇相关文章中，Sudheer 等人强调了 FGF 信号在小鼠 ESC 通过 EpiSC 样状态分化为不同的前体中胚层细胞类型的研究中的重要作用，该研究可能有助于更深入地了解肌肉骨骼早期发育过程中出现的疾病。⁶

细菌和病毒性肺炎和脓毒症是急性呼吸窘迫综合征 (ARDS) 的最常见原因，该综合征仍然是危重患者残疾和死亡的主要原因。⁷由常驻巨噬细胞对感染的反应介导的过度肺部炎症是 ARDS 病理生理学的主要特征。⁸尽管多年来一直在寻找 ARDS 的有效治疗方法，但由于 2019 年冠状病毒病 (COVID-19) 在全球范围内的影响，这一领域最近受到了广泛关注，2019 年冠状病毒病是一种由严重急性呼吸道感染引起的肺炎样疾病。呼吸综合征冠状病毒 2 (SARS-CoV-2)。^{9, 10 名}重症 COVID-19 患者出现过度炎症、过度活跃的免疫反应，引发“细胞因子风暴”，以及可进展为 ARDS 的血栓前状态，据报道患者死亡率超过 50%。^{11 间}充质干细胞 (MSC) 疗法代表了 ARDS 的一种潜在有效的治疗选择，目前正在进行的试验正在评估这种方法在重症 COVID-19 患者中的作用，相关研究试图描绘 MSC 在细菌诱导的急性呼吸窘迫综合征中治疗效果背后的分子机制。疾病的形式。在我们本月发表在STEM CELLS Translational Medicine上的第二篇专题文章中，Lanzoni 等人报告了一项针对新冠肺炎患者的脐带间充质干细胞治疗的双盲、随机、对照、早期临床试验的令人鼓舞的结果。 19 相关 ARDS。¹²在STEM CELLS最近发表的一篇相关文章中，Jackson 等人证明，线粒体转移至巨噬细胞是 MSC 在细菌诱导的 ARDS 中介导其治疗能力的关键机制。¹³