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Construction of induced pluripotent stem cell line (CSBZZUi002-A) from the fibroblast cells of a healthy female 从一名健康女性的成纤维细胞中构建诱导多能干细胞系(CSBZZUi002-A)。
IF 0.8 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-20 DOI: 10.1016/j.scr.2024.103593
We recruited a healthy 44-year-old female and obtained her skin fibroblasts. Subsequently, the induced pluripotent stem cell line was successfully established using non-integrated reprogramming technology. The cell line had a normal karyotype and has been confirmed to have good pluripotency through the detection of pluripotency markers and detection of teratoma formation. This cell line can serve as an effective control for studying the cellular pathological mechanisms of other specific mutations.
我们招募了一名 44 岁的健康女性,并获得了她的皮肤成纤维细胞。随后,我们利用非整合重编程技术成功建立了诱导多能干细胞系。该细胞系核型正常,通过检测多能性标志物和检测畸胎瘤的形成,证实其具有良好的多能性。该细胞系可作为研究其他特定突变的细胞病理机制的有效对照。
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引用次数: 0
Establishing an induced pluripotent stem cell line (SDPHi006-A) from a healthy Chinese female donor represents an accomplishment 从一名健康的中国女性捐献者身上建立诱导多能干细胞系(SDPHi006-A)是一项成就。
IF 0.8 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-20 DOI: 10.1016/j.scr.2024.103590
We isolated peripheral blood mononuclear cells (PBMCs) from a healthy female donor, and successfully converted into induced pluripotent stem cells (iPSCs) by using non-integrating episomal vectors. These iPSCs displayed a normal karyotype, expressed markers of pluripotency, and showed the capacity to differentiate into three germ layers in vitro, which could be utilized for future research endeavors.
我们从一名健康女性捐献者身上分离出外周血单核细胞(PBMC),并利用非整合外显子载体成功将其转化为诱导多能干细胞(iPSC)。这些 iPSCs 显示了正常的核型,表达了多能性标记,并显示了在体外分化成三个生殖层的能力,可用于未来的研究工作。
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引用次数: 0
Establishment of a human-induced pluripotent stem cell line from a long QT syndrome type 2 patient harboring a KCNH2 mutation 从一名携带 KCNH2 突变的长 QT 综合征 2 型患者体内建立人类诱导多能干细胞系。
IF 0.8 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-20 DOI: 10.1016/j.scr.2024.103592
Long QT syndrome type 2 (LQT2) is a heart disorder resulting from a loss-of-function mutation in the KCNH2 gene that causes loss of Kv11.1 channel function, potentially resulting in syncope, arrhythmias, and sudden death. We derived induced pluripotent stem cell line from PBMC of LQT2 patient carrying a variant of pathogenic variant (c.157G > A; p.Gly53Ser). The generation of iPSC lines was achieved using the non-integrative Sendai virus-mediated iPSC reprogramming method. The iPSC cell line exhibit pluripotency, normal karyotype, stem cell morphology, and differentiation capability, resulting a reliable cell source to study the effects of KCNH2 mutation in disease-specific cell types.
长 QT 综合征 2 型(LQT2)是一种因 KCNH2 基因功能缺失突变导致 Kv11.1 通道功能丧失而引起的心脏疾病,可能导致晕厥、心律失常和猝死。我们从携带致病变异体(c.157G > A; p.Gly53Ser)的 LQT2 患者的 PBMC 中提取了诱导多能干细胞系。利用仙台病毒介导的非整合 iPSC 重编程方法生成了 iPSC 细胞系。iPSC 细胞系具有多能性、正常核型、干细胞形态和分化能力,是研究 KCNH2 突变对疾病特异性细胞类型影响的可靠细胞来源。
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引用次数: 0
Establishment of an induced pluripotent stem cell line (SDCHi011-A) from a healthy Chinese female donor 从一名健康的中国女性供体中建立诱导多能干细胞系(SDCHi011-A)。
IF 0.8 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-19 DOI: 10.1016/j.scr.2024.103588
We generated an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells (PBMCs) of a healthy 40-year-old Chinese Han female, using non-integrated reprogramming technology. The established iPSC line, SDCHi011-A, expressed pluripotency marker and could differentiate into cells of three germ layers in vitro with normal karyotype. This cell line is a valuable resource as a control line for stem cell research of disease models and molecular pathogenesis.
我们利用非整合重编程技术,从一名 40 岁健康中国汉族女性的外周血单核细胞(PBMC)中生成了一个诱导多能干细胞(iPSC)系。建立的 iPSC 细胞系 SDCHi011-A 表达了多能性标记,可在体外分化为三个生殖层的细胞,核型正常。该细胞系是疾病模型和分子发病机制干细胞研究的宝贵对照系资源。
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引用次数: 0
Establishment of heterozygous LMOD2 knockout human embryonic stem cell line (ZZUNEUi022-A-1) using CRISPR/Cas9 system 利用 CRISPR/Cas9 系统建立杂合子 LMOD2 基因敲除人类胚胎干细胞系(ZZUNEUi022-A-1)。
IF 0.8 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-19 DOI: 10.1016/j.scr.2024.103586
Dilated Cardiomyopathy (DCM), a prevalent form of cardiomyopathy, is characterized by ventricular dilation and systolic dysfunction. Its etiology is intricate, encompassing multiple genetic and environmental elements. The LMOD2 (Leiomodin 2) gene has been demonstrated to be closely associated with the pathogenesis of DCM. In this study, a pure cell line was generated by knocking out the LMOD2 gene, and a DCM cell model was established through induced differentiation, thus providing a powerful experimental approach for further understanding the pathogenesis of DCM. It also provides a potential research orientation for the early diagnosis and individualized treatment of DCM.
扩张型心肌病(DCM)是一种常见的心肌病,以心室扩张和收缩功能障碍为特征。其病因错综复杂,包括多种遗传和环境因素。LMOD2(Leiomodin 2)基因已被证实与 DCM 的发病机制密切相关。本研究通过敲除 LMOD2 基因产生了纯细胞系,并通过诱导分化建立了 DCM 细胞模型,从而为进一步了解 DCM 的发病机制提供了有力的实验方法。这也为 DCM 的早期诊断和个体化治疗提供了一个潜在的研究方向。
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引用次数: 0
Generation of IPi002-A/B/C human induced pluripotent stem cell lines from MARCH amniotic fluid cells 从 MARCH 羊水细胞中生成 IPi002-A/B/C 人类诱导多能干细胞系。
IF 0.8 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-19 DOI: 10.1016/j.scr.2024.103589
Human induced pluripotent stem cells (hiPSCs) have become a revolutionary tool in biomedical research due to their unique in vitro properties and fate versatility. They offer insights into development or genetic disorders, facilitate drug discovery and hold promise for regenerative medicine. Here we generated three hiPSC cells – IPi002-A/B/C – from primary amniotic fluid cells (AFCs) obtained via amniocentesis for the prenatal diagnosis of MARCH syndrome: Multinucleated neurons, Anhydramnios, Renal dysplasia, Cerebellar hypoplasia, and Hydranencephaly. These AFCs underwent reprogramming through non-integrative viral transduction and the resulting hiPSCs exhibited normal karyotype and expressed typical pluripotency markers.
人类诱导多能干细胞(hiPSCs)因其独特的体外特性和命运多变性,已成为生物医学研究的革命性工具。它们有助于深入了解发育或遗传疾病,促进药物发现,并为再生医学带来希望。在这里,我们从羊膜腔穿刺术获得的原代羊水细胞(AFCs)中生成了三个hiPSC细胞--IPi002-A/B/C,用于MARCH综合征的产前诊断:多核神经元、无羊水、肾发育不良、小脑发育不全和多脑畸形。这些 AFC 通过非整合病毒转导进行了重编程,产生的 hiPSCs 显示出正常的核型并表达典型的多能性标记。
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引用次数: 0
Generation of human induced pluripotent stem cell lines derived from two glucose transporter 1 deficiency syndrome patients 从两名葡萄糖转运体 1 缺乏综合征患者身上提取的人类诱导多能干细胞系的生成
IF 0.8 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-18 DOI: 10.1016/j.scr.2024.103584
Glucose transporter 1 deficiency syndrome (GLUT1DS), caused by impaired glucose transport at the blood–brain barriers, leads to various central nervous system dysfunctions. A comprehensive understanding of the underlying disease pathogenesis is still lacking. In this study, we have generated GLUT1DS-specific human induced pluripotent stem cells (hiPSCs) derived from two patients. These established GLUT1DS-specific hiPSC lines showed self-renewal and pluripotency and carried heterozygous frameshift or missense mutations in the responsible SLC2A1 gene. These novel cell resources provide new avenues for understanding disease mechanisms and developing new therapies for GLUT1DS.
葡萄糖转运体 1 缺乏综合征(GLUT1DS)是由血脑屏障葡萄糖转运障碍引起的,会导致各种中枢神经系统功能障碍。目前对其发病机制还缺乏全面的了解。在这项研究中,我们从两名患者身上获得了 GLUT1DS 特异性人诱导多能干细胞(hiPSCs)。这些已建立的GLUT1DS特异性hiPSC细胞系具有自我更新和多能性,并在负责的SLC2A1基因中携带杂合框移或错义突变。这些新型细胞资源为了解 GLUT1DS 的疾病机制和开发新的疗法提供了新的途径。
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引用次数: 0
Ice recrystallization inhibitors enable efficient cryopreservation of induced pluripotent stem cells: A functional and transcriptomic analysis 冰重结晶抑制剂可实现诱导多能干细胞的高效冷冻保存:功能和转录组分析
IF 0.8 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-18 DOI: 10.1016/j.scr.2024.103583
The successful use of human induced pluripotent stem cells (iPSCs) for research or clinical applications requires the development of robust, efficient, and reproducible cryopreservation protocols. After cryopreservation, the survival rate of iPSCs is suboptimal and cell line-dependent. We assessed the use of ice recrystallization inhibitors (IRIs) for cryopreservation of human iPSCs. A toxicity screening study was performed to assess specific small-molecule carbohydrate-based IRIs and concentrations for further evaluation. Then, a cryopreservation study compared the cryoprotective efficiency of 15 mM IRIs in 5 % or 10 % DMSO-containing solutions and with CryoStor® CS10. Three iPSC lines were cryopreserved as single-cell suspensions in the cryopreservation solutions and post-thaw characteristics, including pluripotency and differential gene expression were assessed. We demonstrate the fitness-for-purpose of 15 mM IRI in 5 % DMSO as an efficient cryoprotective solution for iPSCs in terms of post-thaw recovery, viability, pluripotency, and transcriptomic changes. This mRNA sequencing dataset has the potential to be used for molecular mechanism analysis relating to cryopreservation. Use of IRIs can reduce DMSO concentrations and its associated toxicities, thereby improving the utility, effectiveness, and efficiency of cryopreservation.
要成功地将人类诱导多能干细胞(iPSCs)用于研究或临床应用,就必须制定稳健、高效和可重复的冷冻保存方案。低温保存后,iPSCs 的存活率并不理想,而且与细胞系有关。我们评估了使用冰重结晶抑制剂(IRIs)冷冻保存人类 iPSCs 的情况。我们进行了一项毒性筛选研究,以评估特定的基于碳水化合物的小分子 IRIs 和浓度,供进一步评估。然后,一项冷冻保存研究比较了 15 mM IRIs 在含 5 % 或 10 % DMSO 溶液中以及与 CryoStor® CS10 的冷冻保护效率。三个 iPSC 品系作为单细胞悬浮液在低温保存溶液中进行了低温保存,并评估了解冻后的特征,包括多能性和不同的基因表达。我们从解冻后恢复、存活率、多能性和转录组变化等方面证明,15 mM IRI in 5 % DMSO 是一种高效的 iPSCs 低温保护溶液。该 mRNA 测序数据集有望用于与低温保存相关的分子机制分析。使用 IRIs 可以降低 DMSO 浓度及其相关毒性,从而提高冷冻保存的实用性、有效性和效率。
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引用次数: 0
Patient-derived induced pluripotent stem cells to study non-canonical splicing variants associated with Hypertrophic Cardiomyopathy 研究与肥厚型心肌病相关的非典型剪接变异的患者来源诱导多能干细胞。
IF 0.8 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-16 DOI: 10.1016/j.scr.2024.103582
Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiomyopathy and a leading cause of sudden death. Genetic testing and familial cascade screening play a pivotal role in the clinical management of HCM patients. However, conventional genetic tests primarily focus on the detection of exonic and canonical splice site variation. Oversighting intronic non-canonical splicing variants potentially contributes to a proportion of HCM patients remaining genetically undiagnosed. Here, using a non-integrative reprogramming strategy, we generated induced pluripotent stem cell (iPSC) lines from four individuals carrying one of two variants within intronic regions of MYBPC3: c.1224-52G > A and c.1898-23A > G. Upon differentiation to iPSC-derived cardiomyocytes (iPSC-CMs), mis-spliced mRNAs were identified in cells harbouring these variants. Both abnormal mRNAs contained a premature termination codon (PTC), fitting the criteria for activation of nonsense mediated decay (NMD). However, the c.1898-23A > G transcripts escaped this mRNA quality control mechanism, while the c.1224-52G > A transcripts were degraded. The newly generated iPSC lines represent valuable tools for studying the functional consequences of intronic variation and for translational research aimed at reversing splicing abnormalities to prevent disease progression.
肥厚型心肌病(HCM)是最常见的遗传性心肌病,也是导致猝死的主要原因。基因检测和家族连锁筛查在 HCM 患者的临床治疗中发挥着关键作用。然而,传统的基因检测主要侧重于检测外显子和典型剪接位点变异。对内含子非典型剪接变异的忽视可能会导致一部分 HCM 患者在遗传学上得不到诊断。在此,我们采用非整合重编程策略,从四个携带 MYBPC3 内含子区两个变异之一(c.1224-52G > A 和 c.1898-23A > G)的个体中产生了诱导多能干细胞(iPSC)系。这两种异常 mRNA 都含有过早终止密码子 (PTC),符合无义介导衰变 (NMD) 激活的标准。然而,c.1898-23A > G 转录本逃脱了这种 mRNA 质量控制机制,而 c.1224-52G > A 转录本则被降解。新生成的 iPSC 株系是研究内含子变异的功能性后果和旨在逆转剪接异常以预防疾病进展的转化研究的宝贵工具。
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引用次数: 0
Generation of a control induced pluripotent stem cell line (CBRCULi014-A) derived from the lymphoblastoid cells of a pediatric individual 从儿科个体的淋巴母细胞中生成对照诱导多能干细胞系 (CBRCULi014-A)
IF 0.8 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-16 DOI: 10.1016/j.scr.2024.103587
Lymphoblastoid cell lines serve as a readily and continuous resource for generating induced pluripotent stem cells (iPSCs), enabling the modeling of various genetic disorders in vitro. When investigating congenital and infantile diseases, age-matched controls derived from pediatric individuals are typically necessary, yet they may be scarce or difficult to obtain. Here, the Sendai virus system was employed to introduce reprogramming factors into lymphoblastoid cells derived from an apparently healthy 4-year-old female. The generated iPSCs strongly expressed pluripotency cell markers and displayed robust trilineage differentiation. CBRCULi014-A is therefore a reliable control iPSC line for pediatric disease investigation.
淋巴母细胞系是生成诱导多能干细胞(iPSCs)的一种现成且持续的资源,可对各种遗传疾病进行体外建模。在研究先天性疾病和婴幼儿疾病时,通常需要来自儿科个体的年龄匹配对照,但这些对照可能很少或难以获得。在这里,研究人员利用仙台病毒系统将重编程因子导入来自一名表面上健康的 4 岁女性的淋巴母细胞。生成的 iPSCs 强烈表达多能性细胞标记,并显示出强大的三系分化能力。因此,CBRCULi014-A 是用于儿科疾病研究的可靠对照 iPSC 株系。
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引用次数: 0
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Stem cell research
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