Human Cell最新文献_第2页

Generation of iPSCs line from patient with Singleton-Merten syndrome.

IF 3.4 3区生物学

Human Cell Pub Date : 2025-03-19 DOI: 10.1007/s13577-025-01203-0

Anna Belyaeva, Kseniya Perepelina, Evdokia Kuznetsova, Daria Smirnova, Tatyana Yakovleva, Victoria Turilova, Irina Neganova, Alla Shatrova, Yuliya Fomicheva, Olga Peregudina, Elena Vasichkina, Anna Kostareva, Anna Malashicheva

{"title":"Generation of iPSCs line from patient with Singleton-Merten syndrome.","authors":"Anna Belyaeva, Kseniya Perepelina, Evdokia Kuznetsova, Daria Smirnova, Tatyana Yakovleva, Victoria Turilova, Irina Neganova, Alla Shatrova, Yuliya Fomicheva, Olga Peregudina, Elena Vasichkina, Anna Kostareva, Anna Malashicheva","doi":"10.1007/s13577-025-01203-0","DOIUrl":"https://doi.org/10.1007/s13577-025-01203-0","url":null,"abstract":"Singleton-Merten syndrome (SMS) is a rare genetic condition associated with abnormal calcification and skeletal anomalies. To explore the underlying mechanisms of this disorder, we generated induced pluripotent stem cells (iPSCs) from the blood cells of a patient with SMS. The iPSCs retain the genetic mutation linked to the syndrome, making them a relevant model for studying disease-specific processes. These cells display all key features of pluripotent stem cells, including the expression of characteristic markers, the ability to differentiate into cell types from all three germ layers, and stable growth during passaging. These iPSCs provide a valuable tool for investigating the processes involved in SMS, particularly those leading to abnormal calcification. They also offer a platform for testing potential therapeutic strategies aimed at addressing SMS-related complications. Future work will focus on directing these cells into specific cell types to better understand the pathways involved in the disease and identify possible treatment targets. This study highlights the potential of patient-derived iPSCs for advancing research into rare genetic disorders.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"71"},"PeriodicalIF":3.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Establishment and characterization of novel patient-derived esophageal tumoroids with long-term cultivability.

IF 3.4 3区生物学

Human Cell Pub Date : 2025-03-19 DOI: 10.1007/s13577-025-01206-x

Takashi Urano, Etsuko Yokota, Miki Iwai, Takuro Yukawa, Yoshio Naomoto, Nagio Takigawa, Hideyo Fujiwara, Takashi Akiyama, Minoru Haisa, Takuya Fukazawa, Tomoki Yamatsuji

{"title":"Establishment and characterization of novel patient-derived esophageal tumoroids with long-term cultivability.","authors":"Takashi Urano, Etsuko Yokota, Miki Iwai, Takuro Yukawa, Yoshio Naomoto, Nagio Takigawa, Hideyo Fujiwara, Takashi Akiyama, Minoru Haisa, Takuya Fukazawa, Tomoki Yamatsuji","doi":"10.1007/s13577-025-01206-x","DOIUrl":"https://doi.org/10.1007/s13577-025-01206-x","url":null,"abstract":"Esophageal cancer is an aggressive and fatal disease classified into two distinct histologic types: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). To develop novel therapeutic strategies, it is important to establish preclinical models of esophageal carcinoma. In this study, we successfully established three types of human esophageal cancer organoids (tumoroids) from surgical specimens for long-term culture. Two of the tumoroids were derived from ESCC and one from EAC, which arose from Barrett's esophagus. Whole-exome sequencing revealed that the tumoroids inherited genetic mutations from the parental tumors and patient-derived tumor xenografts closely mimicked the pathology of the original esophageal cancers. In addition to whole-exome analysis, copy number and immunohistochemical analyses demonstrated HER2 expression and amplification as well as HER3 expression and mutation in esophageal tumoroids derived from adenocarcinoma in Barrett's esophagus. HER2-targeting antibody-drug conjugates (ADCs), trastuzumab deruxtecan (T-DXd), and patritumab deruxtecan (P-DXd) effectively suppressed the viability of the tumoroids. Therefore, the establishment of esophageal tumoroids with long-term cultivability makes it possible to obtain reproducible basic data, including drug sensitivity studies, which are important for the development of personalized therapies and treatment strategies.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"72"},"PeriodicalIF":3.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of hepatocellular senescence in the development of hepatocellular carcinoma and the potential for therapeutic manipulation.

IF 3.4 3区生物学

Human Cell Pub Date : 2025-03-18 DOI: 10.1007/s13577-025-01201-2

Pramudi Wijayasiri, Stuart Astbury, Grace Needham, Philip Kaye, Mamatha Bhat, Anna M Piccinini, Aloysious D Aravinthan

{"title":"Role of hepatocellular senescence in the development of hepatocellular carcinoma and the potential for therapeutic manipulation.","authors":"Pramudi Wijayasiri, Stuart Astbury, Grace Needham, Philip Kaye, Mamatha Bhat, Anna M Piccinini, Aloysious D Aravinthan","doi":"10.1007/s13577-025-01201-2","DOIUrl":"10.1007/s13577-025-01201-2","url":null,"abstract":"Accumulation of senescent hepatocytes is universal in chronic liver disease (CLD). This study investigates an association between hepatocyte senescence and hepatocellular carcinoma (HCC) and explores the therapeutic role of sirolimus. Background liver biopsies from 15 patients with cirrhosis and HCC and 45 patients with cirrhosis were stained for p16, a marker of cell senescence. STAM™ mice were randomized into 3 groups of 5 at 4 weeks of age and administered vehicle ± sirolimus intraperitoneally, thrice weekly, from 4 to 18 weeks of age. Placebo group was an administered vehicle, early sirolimus group was an administered vehicle with sirolimus, late sirolimus group was an administered vehicle from 4 to 12 weeks then vehicle with sirolimus from 12 to 18 weeks. The primary outcome was HCC nodule development. Senescent hepatocyte burden and senescence-associated secretory phenotype (SASP) factors were assessed in mice livers. In the human study, age (OR 1.282, 95% CI 1.086-1.513, p = 0.003) and p16 (OR 1.429, 95% CI 1.112-1.838, p = 0.005) were independently associated with HCC. In the animal study, all three groups exhibited similar MASLD activity scores (p = 0.39) and fibrosis area (p = 0.92). The number and the maximum diameter of HCC nodules were significantly lower in the early sirolimus group compared to placebo and late sirolimus group. The gene expression of SASP factors was similar in all groups. Protein levels of some SASP factors (TNFα, IL1β, IL-2, CXCL15) were significantly lower in sirolimus administered groups compared to placebo group. The study demonstrates an independent association between senescent hepatocyte burden and HCC. It indicates a potential chemoprophylactic role for sirolimus through SASP factor inhibition. These early results could inform a future human clinical trial.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"70"},"PeriodicalIF":3.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Derivation of functional neurons from induced pluripotent stem cells using a simple neuromesodermal progenitor generation and rapid spinal cord neuron differentiation process.

IF 3.4 3区生物学

Human Cell Pub Date : 2025-03-13 DOI: 10.1007/s13577-025-01200-3

Selinay Şenkal-Turhan, Ezgi Bulut-Okumuş, Fikrettin Şahin, Yavuz Yavuz, Bayram Yılmaz, Hatice Burcu Şişli, Sadık Kalaycı, Hüseyin Buğra Özgün, Zehra Ömeroğlu Ulu, Pınar Akkuş Süt, Ayşegül Doğan

{"title":"Derivation of functional neurons from induced pluripotent stem cells using a simple neuromesodermal progenitor generation and rapid spinal cord neuron differentiation process.","authors":"Selinay Şenkal-Turhan, Ezgi Bulut-Okumuş, Fikrettin Şahin, Yavuz Yavuz, Bayram Yılmaz, Hatice Burcu Şişli, Sadık Kalaycı, Hüseyin Buğra Özgün, Zehra Ömeroğlu Ulu, Pınar Akkuş Süt, Ayşegül Doğan","doi":"10.1007/s13577-025-01200-3","DOIUrl":"https://doi.org/10.1007/s13577-025-01200-3","url":null,"abstract":"To generate spinal cord neurons from pluripotent stem cells via neuromesodermal progenitors (NMPs) is not only an important step for regenerative purposes but also required for human developmental research. This study describes a protocol to obtain spinal cord neurons in culture using induced pluripotent stem-cell-derived NMPs. The protocol starts with a 3D culture of NMPs and continues with the transfer of 3D NMPs to monolayer culture in which retinoic acid and sonic hedgehog pathways were triggered sequentially. The established protocol enabled generation of spinal cord neurons with active calcium signaling, electrophysiological activity, axon elongation capacity, and synaptic vesicle trafficking. The expression profile of marker proteins, including β-Tubulin, NeuroD1, Pax6, NeuN, Mnx-1, Isl1, Isl2, Map2, NF, Sox2 was detected to explore the production of developmental regulatory transcription factors and terminal differentiation markers in a time-dependent manner. Cells during differentiation process acquired a fully neural phenotype, which was confirmed by RNA sequencing at the molecular level. The protein expression profile showed neural differentiation induction pathways based on LS-MS/MS analysis. Since NMPs differentiate into spinal cord neuron cells at the developmental stage, the results of this study highlight the further potential of NMP-derived spinal cord neurons in disease modeling and treatment in the clinics.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"69"},"PeriodicalIF":3.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vitro generation of spiral ganglion neurons from embryonic stem cells.

IF 3.4 3区生物学

Human Cell Pub Date : 2025-03-12 DOI: 10.1007/s13577-025-01194-y

Oluwafemi S Agboola, Meng Deng, Zhengqing Hu

{"title":"In vitro generation of spiral ganglion neurons from embryonic stem cells.","authors":"Oluwafemi S Agboola, Meng Deng, Zhengqing Hu","doi":"10.1007/s13577-025-01194-y","DOIUrl":"10.1007/s13577-025-01194-y","url":null,"abstract":"Spiral ganglion neurons (SGNs) are crucial for transmitting auditory signals from the inner ear to the brainstem, playing a pivotal role in the peripheral hearing process. However, SGNs are usually damaged by a variety of insults, which causes permanent hearing loss. Generating SGNs from stem cells represents a promising strategy for advancing cell-replacement therapies to treat sensorineural hearing loss. SGNs comprise two subtypes of neurons (types 1 and 2); however, it remains a challenge to regenerate SGN subtypes. This study aimed to investigate the generation and characterization of SGN subtype neurons induced from embryonic stem cells (ESCs) in vitro. ESCs were cultured and treated with retinoic acid, followed by neuronal induction. The differentiated cells showed protein expressions of multiple neuronal markers, suggesting the generation of neuron-like cells. Protein expressions of vGlut-1 and GATA-3 indicate the generation of glutamatergic otic neuron-like cells. ESC-derived neuron-like cells cultured for 6 days showed co-expressions of calretinin, calbindin, and POU4F1 antibodies, suggesting an early stage of SGN subtype induction. However, 14-day in vitro induction generated cells showing two distinct SGN subtypes: a group of cells expressed calretinin (subtype 1a/2 precursor), and the other group expressed calbindin and POU4F1 (subtype 1b/c). These results suggest that in vitro generation of SGN subtypes from ESCs is culture time dependent.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"68"},"PeriodicalIF":3.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Circ_0090100 induces AHNAK expression to inhibit trophoblast cell proliferation and invasion and accelerate cell apoptosis by segregating miR-139-5p in preeclampsia.

IF 3.4 3区生物学

Human Cell Pub Date : 2025-03-10 DOI: 10.1007/s13577-025-01185-z

Zhenli Shan, Linfang Zhou, Yan Ma, Yiying Huang

{"title":"Circ_0090100 induces AHNAK expression to inhibit trophoblast cell proliferation and invasion and accelerate cell apoptosis by segregating miR-139-5p in preeclampsia.","authors":"Zhenli Shan, Linfang Zhou, Yan Ma, Yiying Huang","doi":"10.1007/s13577-025-01185-z","DOIUrl":"https://doi.org/10.1007/s13577-025-01185-z","url":null,"abstract":"The etiology of preeclampsia (PE) is complex and is known to involve the expression of circular RNAs (circRNAs). Among these, the function of circ_0090100 in PE is yet to be fully understood. This study was conducted to examine the expression profile of circ_0090100 in placental tissues from PE patients and to assess its influence on trophoblast cell functions. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the RNA expression levels of circ_0090100, microRNA-139-5p (miR-139-5p), and AHNAK nucleoprotein (AHNAK). Cell viability, proliferation, apoptosis, and invasion were assessed using the CCK-8 assay, EdU incorporation, flow cytometry, and transwell migration assays, respectively. Western blot analysis was performed to detect the protein expression of N-cadherin, Vimentin, and AHNAK. Dualluciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to elucidate the relationships between circ_0090100, miR-139-5p, and AHNAK. We found that the expression of circ_0090100 and AHNAK was upregulated, while miR-139-5p. expression was downregulated in PE placental tissues compared to controls. Transfection of a plasmid overexpressing circ_0090100 into JEG-3 and HTR-8/SVneo trophoblast cell lines resulted in reduced cell proliferation and invasion, but increased apoptosis. Mechanistically, circ_0090100 functioned as a miR-139-5p sponge, and miR-139-5p targeted AHNAK. Furthermore, upregulating miR-139-5p reversed the effects of circ_0090100 in JEG-3 and HTR-8/SVneo cells. AHNAK was found to be involved in the regulation of miR-139-5p effects on trophoblast cells. Additionally, circ_0090100 induced the production of AHNAK through miR-139-5p. Therefore, circ_0090100 activated AHNAK to suppress trophoblast cell proliferation and invasion, and promote cell apoptosis, via miR-139-5p.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"67"},"PeriodicalIF":3.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

STX1A regulates ferroptosis and chemoresistance in gastric cancer through mitochondrial function modulation. STX1A 通过线粒体功能调节胃癌的铁蛋白沉积和化疗耐药性

IF 3.4 3区生物学

Human Cell Pub Date : 2025-03-08 DOI: 10.1007/s13577-025-01195-x

Yan Niu, Chunyu Liu, Lizhou Jia, Fangxin Zhao, Yixiao Wang, Lu Wang, Weiyi Chen, Yanzi Gan, Yongjun Wen

{"title":"STX1A regulates ferroptosis and chemoresistance in gastric cancer through mitochondrial function modulation.","authors":"Yan Niu, Chunyu Liu, Lizhou Jia, Fangxin Zhao, Yixiao Wang, Lu Wang, Weiyi Chen, Yanzi Gan, Yongjun Wen","doi":"10.1007/s13577-025-01195-x","DOIUrl":"10.1007/s13577-025-01195-x","url":null,"abstract":"Gastric cancer is one of the leading causes of cancer-related deaths worldwide, and chemoresistance remains a major obstacle to effective treatment. Ferroptosis, a novel form of regulated cell death, has emerged as a potential therapeutic strategy to treat cancer. However, the molecular mechanisms regulating ferroptosis in gastric cancer remain largely unknown. In this study, we identified syntaxin 1A (STX1A) as a novel regulator of mitochondrial function and ferroptosis in gastric cancer. We found that STX1A is overexpressed in gastric cancer cell lines and tissues and that its knockdown inhibits cell proliferation and induces ferroptosis. Notably, we made the novel discovery that STX1A is localized to the mitochondria, providing a direct link between STX1A and mitochondrial function. Mechanistically, we demonstrated that STX1A depletion impairs mitochondrial respiration, leading to increased oxidative stress and ferroptosis. Furthermore, we showed that targeting STX1A or directly inhibiting mitochondrial function can reverse acquired resistance to 5-fluorouracil and cisplatin in gastric cancer cells by inducing ferroptosis. Our findings provide new insights into the regulation of ferroptosis in gastric cancer and suggest that the STX1A-mitochondria-ferroptosis axis may be a promising therapeutic target for overcoming chemoresistance and improving patient outcomes.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"66"},"PeriodicalIF":3.4,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Replication factor C4, which is regulated by insulin-like growth factor 2 mRNA binding protein 2, enhances the radioresistance of breast cancer by promoting the stemness of tumor cells.

IF 3.4 3区生物学

Human Cell Pub Date : 2025-03-07 DOI: 10.1007/s13577-025-01197-9

Xiao-Yu Zhu, Pi-Song Li, Hui Qu, Xing Ai, Zi-Ting Zhao, Jia-Bei He

{"title":"Replication factor C4, which is regulated by insulin-like growth factor 2 mRNA binding protein 2, enhances the radioresistance of breast cancer by promoting the stemness of tumor cells.","authors":"Xiao-Yu Zhu, Pi-Song Li, Hui Qu, Xing Ai, Zi-Ting Zhao, Jia-Bei He","doi":"10.1007/s13577-025-01197-9","DOIUrl":"https://doi.org/10.1007/s13577-025-01197-9","url":null,"abstract":"Radiotherapy resistance, is usually caused by enhanced tumor stemness and poses a significant challenge in treating breast cancer (BRCA). In this study, we investigated the molecular regulatory mechanism of radiotherapy sensitivity in BRCA associated with replication factor C4 (RFC4) and insulin-like growth factor 2 mRNA binding protein 2 mRNA Binding Protein 2 (IGF2BP2). RFC4 expression was increased in BRCA cell lines and tissues, and high RFC4 expression in BRCA patients predicted the occurrence of lymphatic metastasis. RFC4-specific short hairpin RNA sequences or RFC4 coding sequences were subsequently cloned and inserted into plasmid vectors to downregulate or upregulate RFC4 expression. Knockdown of RFC4 attenuated stemness, as evidenced by a reduction in sphere formation and the downregulation of CD44 and SOX2. RFC4 silencing inhibited migration and invasion, promoted apoptosis, and improved sensitivity to radiotherapy (4-Gy X-ray). The results were detected by a wound healing assay, a transwell assay, and flow cytometry. The overexpression of RFC4 had the opposite effect on BRCA cells. Like RFC4 expression, IGF2BP2 expression was also increased in the cancer tissues of breast cancer patients. The results of the dual luciferase assay and RIP assay confirmed the binding of IGF2BP2 to the RFC4 mRNA coding sequence. Knockdown of RFC4 eliminated the effects of IGF2BP2 overexpression on increasing cell viability, invasion, the expression of stemness markers and radioresistance, suggesting that the effect of RFC4 on the stemness of BRCA cells was regulated by IGF2BP2. In conclusion, we reported that RFC4, a key regulator of BRCA progression, promoted radioresistance in BRCA and was positively regulated by IGF2BP2.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"65"},"PeriodicalIF":3.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel CRISPR-Cas9 iPSC knockouts for PCCA and PCCB genes: advancing propionic acidemia research.

IF 3.4 3区生物学

Human Cell Pub Date : 2025-03-05 DOI: 10.1007/s13577-025-01193-z

Emilio M García-Tenorio, Mar Álvarez, Mónica Gallego-Bonhomme, Lourdes R Desviat, Eva Richard

{"title":"Novel CRISPR-Cas9 iPSC knockouts for PCCA and PCCB genes: advancing propionic acidemia research.","authors":"Emilio M García-Tenorio, Mar Álvarez, Mónica Gallego-Bonhomme, Lourdes R Desviat, Eva Richard","doi":"10.1007/s13577-025-01193-z","DOIUrl":"10.1007/s13577-025-01193-z","url":null,"abstract":"Propionic acidemia (PA) is a rare autosomal recessive metabolic disorder caused by mutations in the PCCA and PCCB genes, which encode subunits of the mitochondrial enzyme propionyl-CoA carboxylase (PCC). This enzyme deficiency leads to the accumulation of toxic metabolites, resulting in severe metabolic dysfunction. To create ideal in vitro disease models of PA with isogenic controls and provide a robust platform for therapeutic research, we generated two induced pluripotent stem cell (iPSC) lines with knockout (KO) mutations in the PCCA and PCCB genes using CRISPR-Cas9 gene editing in a healthy control iPSC line. The KO iPS cells were successfully established and characterized, confirming the presence of frameshift insertions and deletions in each target gene, as well as the loss of the corresponding transcript, protein expression, and activity. Additionally, the generated iPSC lines exhibit hallmark characteristics of pluripotency, including the potential to differentiate into all three germ layers. Our PCCA and PCCB KO iPSC models provide a valuable tool for studying the molecular mechanisms underlying PA and hold potential for advancing new therapeutic approaches.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"64"},"PeriodicalIF":3.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Poly(I:C) signaling induces robust CXCL10 production and apoptosis in human esophageal squamous cell carcinoma cells.

IF 3.4 3区生物学

Human Cell Pub Date : 2025-03-03 DOI: 10.1007/s13577-025-01191-1

Yusuke Sato, Akari Yamaya, Kento Sonoda, Akiyuki Wakita, Yushi Nagaki, Ryohei Sasamori, Yoshihiro Sasaki, Takatoshi Yoneya, Shu Nozaki, Tsukasa Takahashi, Misako Matsumoto, Tsukasa Seya, Kazuhiro Imai

{"title":"Poly(I:C) signaling induces robust CXCL10 production and apoptosis in human esophageal squamous cell carcinoma cells.","authors":"Yusuke Sato, Akari Yamaya, Kento Sonoda, Akiyuki Wakita, Yushi Nagaki, Ryohei Sasamori, Yoshihiro Sasaki, Takatoshi Yoneya, Shu Nozaki, Tsukasa Takahashi, Misako Matsumoto, Tsukasa Seya, Kazuhiro Imai","doi":"10.1007/s13577-025-01191-1","DOIUrl":"10.1007/s13577-025-01191-1","url":null,"abstract":"We previously reported that high tumoral expression of Toll-like receptor 3 (TLR3) and CXCL10, a member of the CXC chemokine family, was an independent positive prognostic factor in patients with advanced thoracic esophageal squamous cell carcinoma (ESCC). However, the direct relationships between TLR3 and CXCL10 in ESCC cells was not fully understood. Here, we analyzed TLR3 mRNA and protein expression in two ESCC lines (TE8 and KYSE180) and one esophageal adenocarcinoma (EAC) line (OE19). We also assessed the effect of the TLR3 agonist poly(I:C) on production of downstream adapter proteins and cytokines, including CXCL10, and further tested its effects on cell viability and caspase 3/7 activity with and without siRNA-induced knockdown of TLR3 and the TICAM-1 or MAVS adapter protein. Both ESCC lines, but not the EAC line, showed high expression of TLR3 mRNA and protein. TICAM-1 and MAVS were also expressed, and their knockdown suppressed responsiveness to poly(I:C) in the ESCC lines. Poly(I:C) induced strong CXCL10 production, resulting in significantly upregulated caspase3/7 activity and downregulated cell proliferation in both ESCC lines but not the EAC line. The effect of poly(I:C) on CXCL10 production was attenuated after transfecting the cells with siRNAs targeting TICAM-1 or MAVS. TLR3 is thus highly expressed in ESCC cells, where it induces strong CXCL10 production and significantly upregulates caspase3/7 activity and downregulates cell proliferation. TLR3 signaling and the resultant downstream CXCL10 production have the potential to serve as useful prognostic markers and therapeutic targets for the treatment of ESCC.","PeriodicalId":49194,"journal":{"name":"Human Cell","volume":"38 3","pages":"63"},"PeriodicalIF":3.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0