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MicroRNA26a Overexpression Hastens Osteoblast Differentiation Capacity in Dental Stem Cells. 过表达 MicroRNA26a 可加快牙科干细胞的成骨细胞分化能力
IF 1.6 4区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-06-01 Epub Date: 2023-05-18 DOI: 10.1089/cell.2023.0004
Steven Kaufman, Peter Chang, Elisha Pendleton, Nalini Chandar

Dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHED) are a source of mesenchymal stem cells with the potential to differentiate into several cell types. We initially isolated SHED cells and compared their osteogenic capacity with commercially available DPSCs. Both cells exhibited similar capacities of growth and osteogenic differentiation. A fourfold to sixfold increase in endogenous microRNA26a (miR26a) expression during osteogenic differentiation of preosteoblasts and a similar but attenuated increase (twofold to fourfold) in differentiating SHED was observed, suggesting a role in the process. We, therefore, overexpressed miR26a in SHED to determine if the osteogenic differentiation capacity can be potentiated in vitro. SHED with a threefold increase in miR26a expression showed increased growth rate when compared with parent cells. When exposed to an osteogenic differentiating promoting medium, the miR26a overexpressing cells showed 100-fold increases in the expression of bone marker genes such as type 1 collagen, alkaline phosphatase, and Runx2. The mineralization capacity of these cells was also increased 15-fold. As miR26a targets regulate several bone-specific genes, we evaluated the effect of miR26a overexpression on established targets. We found a moderate decrease in SMAD1 and a profound decrease in PTEN expression. miR26a could potentiate its effect on osteoblast differentiation by its ability to inhibit PTEN and increase the viability of cells and their numbers, a process essential in osteoblast differentiation. Our studies suggest that the upregulation of miR26a can increase bone formation and may serve as an important target to further investigate its potential in tissue engineering applications.

牙髓干细胞(DPSCs)和来自人类脱落牙齿(SHED)的干细胞是间充质干细胞的一种来源,具有分化成多种细胞类型的潜力。我们最初分离了SHED细胞,并将其成骨能力与市售的DPSC细胞进行了比较。两种细胞的生长和成骨分化能力相似。在前成骨细胞的成骨分化过程中,观察到内源性microRNA26a(miR26a)的表达增加了四至六倍,而在分化的SHED中,内源性microRNA26a(miR26a)的表达也有类似的增加(两倍至四倍),但幅度较小,这表明miR26a在成骨分化过程中发挥作用。因此,我们在 SHED 中过表达 miR26a,以确定能否在体外增强成骨分化能力。与母细胞相比,miR26a 表达量增加三倍的 SHED 的生长速度加快。在成骨分化促进培养基中,miR26a 过表达细胞的骨标记基因(如 1 型胶原蛋白、碱性磷酸酶和 Runx2)表达量增加了 100 倍。这些细胞的矿化能力也提高了 15 倍。由于 miR26a 的靶标调控多个骨特异性基因,我们评估了 miR26a 过表达对既定靶标的影响。我们发现 SMAD1 的表达中度下降,而 PTEN 的表达则大幅下降。miR26a 可通过抑制 PTEN 的能力增强其对成骨细胞分化的影响,并提高细胞的活力和数量,而这正是成骨细胞分化的一个必要过程。我们的研究表明,miR26a 的上调可增加骨形成,可作为一个重要靶点,进一步研究其在组织工程应用中的潜力。
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引用次数: 0
Reprogramming Stars #12: At the Heart of In Vivo Reprogramming- An Interview with Dr. Li Qian. 重编程之星#12:体内重编程的核心——李茜博士访谈录
IF 1.6 4区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-06-01 DOI: 10.1089/cell.2023.0056
Li Qian, Carlos-Filipe Pereira
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引用次数: 0
Evaluation of All Human Transcription Factors on the Directed Differentiation of Pluripotent Stem Cells. 所有人转录因子对多能干细胞定向分化的影响。
IF 1.6 4区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-04-01 DOI: 10.1089/cell.2023.0007
Rodrigo L Dos Santos
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引用次数: 0
Treatments of Porcine Nuclear Recipient Oocytes and Somatic Cell Nuclear Transfer-Generated Embryos with Various Reactive Oxygen Species Scavengers Lead to Improvements of Their Quality Parameters and Developmental Competences by Mitigating Oxidative Stress-Related Impacts. 用各种活性氧清除剂处理猪核受体卵母细胞和体细胞核移植胚胎,通过减轻氧化应激相关的影响,改善其质量参数和发育能力。
IF 1.6 4区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-04-01 DOI: 10.1089/cell.2022.0145
Seung-Hwan Oh, Seung-Eun Lee, Dong-Hun Han, Jae-Wook Yoon, So-Hee Kim, Eun-Seo Lim, Han-Bi Lee, Eun-Young Kim, Se-Pill Park

This study investigated the antioxidant effects of β-cryptoxanthin (BCX), hesperetin (HES), and icariin (ICA), and their effects on in vitro maturation of porcine oocytes and subsequent embryonic development of somatic cell nuclear transfer (SCNT). Treatment with 1 μM BCX (BCX-1) increased the developmental rate of porcine oocytes more than treatment with 100 μM HES (HES-100) or 5 μM ICA (ICA-5). The glutathione level and mRNA expression of antioxidant genes (NFE2L2, SOD1, and SOD2) were more increased in the BCX-1 group than in the HES-100 and ICA-5 groups, while the reactive oxygen species level was more decreased. Moreover, BCX improved the developmental capacity and quality of SCNT embryos. The total cell number, apoptotic cell rate, and development-related gene expression were modulated in the BCX-1 group to enhance embryonic development of SCNT. These results show that the antioxidant effects of BCX enhance in vitro maturation of porcine oocytes and subsequent embryonic development of SCNT.

本研究探讨了β-隐黄质(BCX)、hesperetin (HES)和淫羊藿苷(ICA)的抗氧化作用及其对猪卵母细胞体外成熟和体细胞核移植(SCNT)胚胎发育的影响。1 μM BCX (BCX-1)处理比100 μM HES (HES-100)和5 μM ICA (ICA-5)处理更能提高猪卵母细胞的发育率。BCX-1组的谷胱甘肽水平和抗氧化基因(NFE2L2、SOD1、SOD2) mRNA表达量明显高于HES-100和ICA-5组,活性氧水平明显低于ha -5组。此外,BCX还能提高SCNT胚胎的发育能力和发育质量。通过调节BCX-1组细胞总数、凋亡细胞率和发育相关基因表达,促进SCNT胚胎发育。这些结果表明,BCX的抗氧化作用促进了猪卵母细胞的体外成熟和SCNT的胚胎发育。
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引用次数: 0
The Emerging Biological Functions of Exosomes from Dental Tissue-Derived Mesenchymal Stem Cells. 牙组织来源间充质干细胞外泌体的新生物学功能。
IF 1.6 4区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-04-01 DOI: 10.1089/cell.2022.0147
Shu Ma, Yidi Jiang, Yuyan Qian, Jing Du, Xiaoyan Yu, Shiyi Luo, Zhu Chen

Exosomes are one kind of small-cell extracellular membranous vesicles that can regulate intercellular communication and give rise to mediating the biological behaviors of cells, involving in tissue formation, repair, the modulation of inflammation, and nerve regeneration. The abundant kinds of cells can secret exosomes, among them, mesenchymal stem cells (MSCs) are very perfect cells for mass production of exosomes. Dental tissue-derived mesenchymal stem cells (DT-MSCs), including dental pulp stem cells, stem cells from exfoliated deciduous teeth, stem cells from apical papilla, stem cells from human periodontal ligament (PDLSCs), gingiva-derived mesenchymal stem cells, dental follicle stem cells, tooth germ stem cells, and alveolar bone-derived mesenchymal stem cells, are now known as a potent tool in the area of cell regeneration and therapy, more importantly, DT-MSCs can also release numerous types of exosomes, participating in the biological functions of cells. Hence, we briefly depict the characteristics of exosomes, give a detailed description of the biological functions and clinical application in some respects of exosomes from DT-MSCs through systematically reviewing the latest evidence, and provide a rationale for their use as tools for potential application in tissue engineering.

外泌体是一类小细胞胞外膜囊,可调节细胞间通讯,介导细胞的生物学行为,参与组织形成、修复、炎症调节和神经再生等。可以分泌外泌体的细胞种类繁多,其中间充质干细胞(MSCs)是大量分泌外泌体的理想细胞。牙组织源性间充质干细胞(DT-MSCs),包括牙髓干细胞、脱落乳牙干细胞、根尖乳头干细胞、人牙周韧带干细胞、牙龈源性间充质干细胞、牙毛囊干细胞、牙胚干细胞和牙槽骨源性间充质干细胞,是目前公认的细胞再生和治疗领域的有力工具。DT-MSCs还可以释放多种类型的外泌体,参与细胞的生物学功能。因此,我们简要描述了外泌体的特征,通过系统回顾最新证据,详细描述了DT-MSCs外泌体的生物学功能和某些方面的临床应用,并为其作为潜在的组织工程应用工具提供了理论依据。
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引用次数: 1
Reprogramming Stars #11: Teaming Up to Uncover the Epitranscriptomics of Reprogramming-An Interview with Dr. Miguel Fidalgo and Dr. Diana Guallar. 重编程之星》第11期:联手揭示重编程的外转录组学--专访米格尔-菲达尔戈博士和戴安娜-瓜拉尔博士。
IF 1.6 4区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-04-01 DOI: 10.1089/cell.2023.0024
Miguel Fidalgo, Diana Guallar, Carlos-Filipe Pereira
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引用次数: 0
A Fundamental Research in In Vitro Spermatogonial Stem Cell Culturing: What Are Clump Cells? 精原干细胞体外培养的基础研究:什么是团块细胞?
IF 1.6 4区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-04-01 DOI: 10.1089/cell.2022.0123
Kiana Sojoudi, Hossein Azizi, Thomas Skutella

Spermatogonial stem cells (SSCs) are a small group of testicular cells located in the basement membrane of seminiferous tubules and can balance self-renewal and differentiation during spermatogenesis. Our in vitro culture experiments of mouse SSCs indicated heterogeneity of cultured cells. Highly compact colonies were observed next to SSC colonies, which we call clump cells. We used immunocytochemical staining to identify SSCs and somatic cells with VASA and Vimentin antibodies. Subsequently, we compared mRNA expression levels of VASA, DAZL, PLZF, GFRA1, Lin28, Kit, Myc and Vimentin genes using Fluidigm real-time RT-polymerase chain reaction in clump cells, SSCs, and testicular stromal cells. To better understand the functions of selected genes, we created a protein-protein interaction network and performed an enrichment analysis using different databases. Based on the data collected, we state that clump cells do not express the molecular markers of SSCs, so we cannot consider them as SSCs; however, we claim that these cells are altered SSCs. The molecular mechanism of this conversion is still obscure. Therefore, this study can support the analysis of germ cell development both in vitro and in vivo. In addition, it can be effective in finding new and more efficient treatments for male infertility.

精原干细胞(SSCs)是一小群位于精小管基底膜的睾丸细胞,在精子发生过程中起着自我更新和分化的平衡作用。小鼠ssc体外培养实验表明,培养细胞具有异质性。在SSC菌落旁边观察到高度紧密的菌落,我们称之为块状细胞。我们用免疫细胞化学染色方法鉴定SSCs和带有VASA和Vimentin抗体的体细胞。随后,我们使用Fluidigm实时rt -聚合酶链反应比较了VASA、DAZL、PLZF、GFRA1、Lin28、Kit、Myc和Vimentin基因在团块细胞、ssc和睾丸间质细胞中的mRNA表达水平。为了更好地了解所选基因的功能,我们创建了一个蛋白质-蛋白质相互作用网络,并使用不同的数据库进行了富集分析。根据收集到的数据,我们认为团块细胞不表达ssc的分子标记,因此我们不能将其视为ssc;然而,我们声称这些细胞是改变的ssc。这种转化的分子机制尚不清楚。因此,本研究可为体外和体内生殖细胞发育分析提供支持。此外,它可以有效地寻找新的和更有效的治疗男性不育症。
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引用次数: 1
Reprogramming Stars #10: Modeling Cancer with Cellular Reprogramming-An Interview with Dr. Dung-Fang Lee. 重编程明星 #10:用细胞重编程模拟癌症--专访 Dung-Fang Lee 博士。
IF 1.6 4区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-02-01 Epub Date: 2023-01-31 DOI: 10.1089/cell.2023.29081.dfl
Dung-Fang Lee, Carlos-Filipe Pereira
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引用次数: 0
Early Life Reprogramming-Based Treatment Promotes Longevity. 基于生命早期重编程的治疗促进长寿。
IF 1.6 4区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-02-01 Epub Date: 2022-12-30 DOI: 10.1089/cell.2022.0153
Patrizia Pessina, Bruno Di Stefano

Short-term expression of Yamanaka factors early in life promotes epigenetic reprogramming and an increased healthy lifespan in a mouse model of accelerated aging.

在小鼠加速衰老模型中,生命早期短期表达山中因子可促进表观遗传学重编程并延长健康寿命。
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引用次数: 0
The Wisdom in Teeth: Neuronal Differentiation of Dental Pulp Cells. 牙齿中的智慧:牙髓细胞的神经元分化。
IF 1.6 4区 医学 Q3 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-02-01 DOI: 10.1089/cell.2022.0102
Bendegúz Sramkó, Anna Földes, Kristóf Kádár, Gábor Varga, Ákos Zsembery, Karolina Pircs

Mesenchymal stem/stromal cells (MSCs) are found in almost all postnatal organs. Under appropriate environmental cues, multipotency enables MSCs to serve as progenitors for several lineage-specific, differentiated cell types. In vitro expansion and differentiation of MSCs give the opportunity to obtain hardly available somatic cells, such as neurons. The neurogenic potential of MSCs makes them a promising, autologous source to restore damaged tissue and as such, they have received much attention in the field of regenerative medicine. Several stem cell pool candidates have been studied thus far, but only a few of them showed neurogenic differentiation potential. Due to their embryonic ontology, stem cells residing in the stroma of the dental pulp chamber are an exciting source for in vitro neural cell differentiation. In this study, we review the key properties of dental pulp stem cells (DPSCs), with a particular focus on their neurogenic potential. Moreover, we summarize the various presently available methods used for neural differentiation of human DPSCs also emphasizing the difficulties in reproducibly high production of such cells. We postulate that because DPSCs are stem cells with very close ontology to neurogenic lineages, they may serve as excellent targets for neuronal differentiation in vitro and even for direct reprogramming.

间充质干细胞/基质细胞(MSCs)几乎存在于所有出生后器官中。在适当的环境提示下,多能性使MSCs能够作为几种谱系特异性分化细胞类型的祖细胞。骨髓间充质干细胞的体外扩增和分化为获得难以获得的体细胞(如神经元)提供了机会。间充质干细胞的神经源性使其成为修复受损组织的一种有前途的自体来源,因此在再生医学领域受到了广泛的关注。到目前为止,已经研究了几个候选干细胞库,但只有少数干细胞显示出神经源性分化潜力。由于其胚胎本体,居住在牙髓腔基质中的干细胞是体外神经细胞分化的一个令人兴奋的来源。在这项研究中,我们回顾了牙髓干细胞(DPSCs)的关键特性,特别关注它们的神经源性潜力。此外,我们总结了目前用于人类DPSCs神经分化的各种可用方法,并强调了可重复高产量这种细胞的困难。我们假设,由于DPSCs是与神经源性谱系非常接近的干细胞,它们可能成为体外神经元分化甚至直接重编程的绝佳靶点。
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引用次数: 4
期刊
Cellular reprogramming
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