Stem cells and development最新文献

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Human-Induced Hepatocytes-Derived Extracellular Vesicles Ameliorated Liver Fibrosis in Mice Via Suppression of TGF-β1/Smad Signaling and Activation of Nrf2/HO-1 Signaling. 人诱导的肝细胞衍生的细胞外小泡通过抑制TGF-β1/Smad信号传导和激活Nrf2/HO-1信号传导改善小鼠肝纤维化。
IF 4 3区 医学
Stem cells and development Pub Date : 2023-10-01 Epub Date: 2023-07-24 DOI: 10.1089/scd.2023.0110
Wenjing Liu, Jiajun Wu, Huiying Cao, Chen Ma, Zhitao Wu, Youxi Tian, Chenhui Ma, Hong Qiu, Guoyu Pan
{"title":"Human-Induced Hepatocytes-Derived Extracellular Vesicles Ameliorated Liver Fibrosis in Mice Via Suppression of TGF-β1/Smad Signaling and Activation of Nrf2/HO-1 Signaling.","authors":"Wenjing Liu,&nbsp;Jiajun Wu,&nbsp;Huiying Cao,&nbsp;Chen Ma,&nbsp;Zhitao Wu,&nbsp;Youxi Tian,&nbsp;Chenhui Ma,&nbsp;Hong Qiu,&nbsp;Guoyu Pan","doi":"10.1089/scd.2023.0110","DOIUrl":"10.1089/scd.2023.0110","url":null,"abstract":"<p><p>Liver fibrosis is a wound-healing response caused by persistent liver injury and often occurs in chronic liver diseases. Effective treatments for liver fibrosis are still pending. Recent studies have revealed that extracellular vesicles (EVs) derived from primary hepatocytes (Hep-EVs) have therapeutic potential for multiple liver diseases. However, Hep-EVs are difficult to manufacture in bulk because of the limited sources of primary hepatocytes. Human-induced hepatocytes (hiHep) are hepatocyte-like cells that can expand in vitro, and their cell culture supernatant is thus an almost unlimited resource for EVs. This study aimed to investigate the potential therapeutic effects of EVs derived from hiHeps. hiHep-EVs inhibited the expression of inflammatory genes and the secretion of inflammation-related cytokines, and suppressed the activation of hepatic stellate cells by inhibiting the transforming growth factor (TGF)-β1/Smad signaling pathway. The anti-inflammatory and antifibrotic effects of hiHep-EVs were similar to those of mesenchymal stem cell-EVs. Furthermore, the administration of hiHep-EVs ameliorated oxidative stress, inflammation, and fibrosis in a CCl<sub>4</sub>-induced liver fibrosis mouse model. The expression of α smooth muscle actin, collagen I, and collagen III was reduced, which may be attributed to the regulation of matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 by hiHep-EVs, and the protein expression of Nrf2, HO-1, and NQO1 was increased. Taken together, our results suggested that hiHep-EVs alleviated liver fibrosis by activating the Nrf2/HO-1 signaling pathway and inhibiting the TGF-β1/Smad signaling pathway. This study revealed the hepatoprotective effect of hiHep-EVs, and provided a new approach to treating liver fibrosis.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":" ","pages":"638-651"},"PeriodicalIF":4.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9856263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Small Extracellular Vesicles Maintain Homeostasis of Senescent Mesenchymal Stem Cells at Least Through Excreting Harmful Lipids. 细胞外小泡至少通过排泄有害脂质维持衰老间充质干细胞的稳态。
IF 4 3区 医学
Stem cells and development Pub Date : 2023-09-01 DOI: 10.1089/scd.2023.0079
Liping Wang, Huan Zhang, Xian Xiao, Shihua Wang, Robert Chunhua Zhao
{"title":"Small Extracellular Vesicles Maintain Homeostasis of Senescent Mesenchymal Stem Cells at Least Through Excreting Harmful Lipids.","authors":"Liping Wang,&nbsp;Huan Zhang,&nbsp;Xian Xiao,&nbsp;Shihua Wang,&nbsp;Robert Chunhua Zhao","doi":"10.1089/scd.2023.0079","DOIUrl":"https://doi.org/10.1089/scd.2023.0079","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) play an essential role in multiple physiological processes in vivo and a promising cell-based therapy for various diseases. Nonetheless, MSCs suffer from senescence with expansion culture, leading to a limitation for their clinical application. Recently, it was reported that small extracellular vesicles (sEVs) are involved in regulation of senescence in tumor cells and fibroblasts. However, the biological roles of sEVs in senescent MSCs (Sen MSCs) are poorly understood. In this study, we established a replicative senescence model of MSCs by successive passages and compared the phenotypic changes between presenescent MSCs (Pre-Sen MSCs) and Sen MSCs and found that Sen MSCs exhibited a diminished adipogenic and osteogenic differentiation potential and elevated senescence-associated secretory phenotype levels. In addition, we found that sEV secretion was increased in Sen MSCs, and inhibition of sEV secretion led to apoptosis, DNA damage, and decreased cell viability, suggesting that increased sEV secretion plays an important role in maintaining Sen MSC homeostasis. To further investigate the molecular mechanisms, metabolomic profiling of Pre-Sen MSC-derived sEVs (Pre-Sen-sEVs) and Sen MSC-derived sEVs (Sen-sEVs) was performed. The results showed that lipid metabolites were significantly increased in Sen-sEVs and these significantly upregulated lipid metabolites were shown to be toxic for inducing cellular senescence and apoptosis in previous studies. Kyoto Encyclopedia of Genes and Genomes analysis revealed enrichment of differential metabolites between Pre-Sen-sEVs and Sen-sEVs mainly in 25 signaling pathways, of which 21 metabolic pathways have been shown to be closely associated with senescence. Taken together, our findings suggested that increased sEV secretion maintains Sen MSC homeostasis, at least in part, by excreting harmful lipids, thus providing new insights into the regulation of senescence by sEVs.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":"32 17-18","pages":"565-579"},"PeriodicalIF":4.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10209722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Blastocyst Cell Number and Allocation Affect the Developmental Potential and Transcriptome of Bovine Somatic Cell Nuclear Transfer Embryos. 囊胚细胞数量和分配对牛体细胞核移植胚胎发育潜能和转录组的影响。
IF 4 3区 医学
Stem cells and development Pub Date : 2023-09-01 DOI: 10.1089/scd.2022.0292
Pablo J Ross, Marcelo D Goissis, João P N Martins, James L Chitwood, J Richard Pursley, Guilherme J M Rosa, Jose B Cibelli
{"title":"Blastocyst Cell Number and Allocation Affect the Developmental Potential and Transcriptome of Bovine Somatic Cell Nuclear Transfer Embryos.","authors":"Pablo J Ross,&nbsp;Marcelo D Goissis,&nbsp;João P N Martins,&nbsp;James L Chitwood,&nbsp;J Richard Pursley,&nbsp;Guilherme J M Rosa,&nbsp;Jose B Cibelli","doi":"10.1089/scd.2022.0292","DOIUrl":"https://doi.org/10.1089/scd.2022.0292","url":null,"abstract":"<p><p>Cloning cattle using somatic cell nuclear transfer (SCNT) is inefficient. Although the rate of development of SCNT embryos in vitro is similar to that of fertilized embryos, most fail to develop into healthy calves. In this study, we aimed to identify developmentally competent embryos according to blastocyst cell composition and perform transcriptome analysis of single embryos. Transgenic SCNT embryos expressing nuclear-localized HcRed gene at day 7 of development were imaged by confocal microscopy for cell counting and individually transferred to recipient heifers. Pregnancy rates were determined by ultrasonography. Embryos capable of establishing pregnancy by day 35 had an average of 117 ± 6 total cells, whereas embryos with an average of 128 ± 5 cells did not establish pregnancy (<i>P</i> < 0.05). A lesser average number of 41 ± 3 cells in the inner cell mass (ICM) also resulted in pregnancies (<0.05) than a greater number of 48 ± 2 cells in the ICM. Single embryos were then subjected to RNA sequencing for transcriptome analysis. Using weighted gene coexpression network analysis, we identified clusters of genes in which gene expression correlated with the number of total cells or ICM cells. Gene ontology analysis of these clusters revealed enriched biological processes in coenzyme metabolic process, intracellular signaling cascade, and glucose catabolic process, among others. We concluded that SCNT embryos with fewer total and ICM cell numbers resulted in greater pregnancy establishment rates and that these differences are reflected in the transcriptome of such embryos.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":"32 17-18","pages":"515-523"},"PeriodicalIF":4.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10198087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to: In Vitro Transdifferentiation Potential of Equine Mesenchymal Stem Cells into Schwann-Like Cells, by Lucas Vinícius de Oliveira Ferreira et al. Stem Cells and Development 2023;32(13-14):422-432; doi: 10.1089/scd.2022.0274. 更正:Lucas Vinícius de Oliveira Ferreira 等人撰写的《马间充质干细胞向许旺样细胞的体外转分化潜能》。 干细胞与发育》2023;32(13-14):422-432; doi: 10.1089/scd.2022.0274。
IF 4 3区 医学
Stem cells and development Pub Date : 2023-09-01 Epub Date: 2023-08-16 DOI: 10.1089/scd.2022.0274.correx
{"title":"<i>Correction to:</i> In Vitro Transdifferentiation Potential of Equine Mesenchymal Stem Cells into Schwann-Like Cells, by Lucas Vinícius de Oliveira Ferreira et al. Stem Cells and Development 2023;32(13-14):422-432; doi: 10.1089/scd.2022.0274.","authors":"","doi":"10.1089/scd.2022.0274.correx","DOIUrl":"10.1089/scd.2022.0274.correx","url":null,"abstract":"","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":"32 17-18","pages":"580"},"PeriodicalIF":4.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11079606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10180761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification and Functional Evaluation of Alternative Splice Variants of Dax1 in Mouse Embryonic Stem Cells. 小鼠胚胎干细胞中Dax1选择性剪接变异体的鉴定和功能评价。
IF 4 3区 医学
Stem cells and development Pub Date : 2023-09-01 Epub Date: 2023-07-14 DOI: 10.1089/scd.2023.0037
Jiaqi Wang, Yi Huang, Chen Zhang, Yan Ruan, Yanping Tian, Fengsheng Wang, Yixiao Xu, Meng Yu, Jiangjun Wang, Yuda Cheng, Lianlian Liu, Ran Yang, Jiali Wang, Yi Yang, Jiaxiang Xiong, Yan Hu, Rui Jian, Bing Ni, Wei Wu, Junlei Zhang
{"title":"Identification and Functional Evaluation of Alternative Splice Variants of Dax1 in Mouse Embryonic Stem Cells.","authors":"Jiaqi Wang,&nbsp;Yi Huang,&nbsp;Chen Zhang,&nbsp;Yan Ruan,&nbsp;Yanping Tian,&nbsp;Fengsheng Wang,&nbsp;Yixiao Xu,&nbsp;Meng Yu,&nbsp;Jiangjun Wang,&nbsp;Yuda Cheng,&nbsp;Lianlian Liu,&nbsp;Ran Yang,&nbsp;Jiali Wang,&nbsp;Yi Yang,&nbsp;Jiaxiang Xiong,&nbsp;Yan Hu,&nbsp;Rui Jian,&nbsp;Bing Ni,&nbsp;Wei Wu,&nbsp;Junlei Zhang","doi":"10.1089/scd.2023.0037","DOIUrl":"10.1089/scd.2023.0037","url":null,"abstract":"<p><p>Dax1 (<i>Nr0b1</i>; Dosage-sensitive sex reversal-adrenal hypoplasia congenital on the X-chromosome gene-1) is an important component of the transcription factor network that governs pluripotency in mouse embryonic stem cells (ESCs). Functional evaluation of alternative splice variants of pluripotent transcription factors has shed additional insight on the maintenance of ESC pluripotency and self-renewal. Dax1 splice variants have not been identified and characterized in mouse ESCs. We identified 18 new transcripts of <i>Dax1</i> with putative protein-coding properties and compared their protein structures with known Dax1 protein (Dax1-472). The expression pattern analysis showed that the novel isoforms were cotranscribed with Dax1-472 in mouse ESCs, but they had transcriptional heterogeneity among single cells and the subcellular localization of the encoded proteins differed. Cell function experiments indicated that Dax1-404 repressed <i>Gata6</i> transcription and functionally replaced Dax1-472, while Dax1-38 and Dax1-225 partially antagonized Dax1-472 transcriptional repression. This study provided a comprehensive characterization of the Dax1 splice variants in mouse ESCs and suggested complex effects of Dax1 variants in a self-renewal regulatory network.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":"32 17-18","pages":"554-564"},"PeriodicalIF":4.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10207593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Apelin-Overexpressing Neural Stem Cells in Conjunction with a Silk Fibroin Nanofiber Scaffold for the Treatment of Traumatic Brain Injury. 过表达apelin的神经干细胞联合丝素纳米纤维支架治疗创伤性脑损伤。
IF 4 3区 医学
Stem cells and development Pub Date : 2023-09-01 DOI: 10.1089/scd.2023.0008
Tianwen Li, Qisheng Tang, Jiaxin Xu, Xiangru Ye, Kezhu Chen, Junjie Zhong, Jianhong Zhu, Shijun Lu, Tongming Zhu
{"title":"Apelin-Overexpressing Neural Stem Cells in Conjunction with a Silk Fibroin Nanofiber Scaffold for the Treatment of Traumatic Brain Injury.","authors":"Tianwen Li,&nbsp;Qisheng Tang,&nbsp;Jiaxin Xu,&nbsp;Xiangru Ye,&nbsp;Kezhu Chen,&nbsp;Junjie Zhong,&nbsp;Jianhong Zhu,&nbsp;Shijun Lu,&nbsp;Tongming Zhu","doi":"10.1089/scd.2023.0008","DOIUrl":"https://doi.org/10.1089/scd.2023.0008","url":null,"abstract":"<p><p>Traumatic brain injury (TBI), especially moderate or severe TBI, is one of the most devastating injuries to the nervous system, as the existing therapies for neurological defect repair have difficulty achieving satisfactory results. Neural stem cells (NSCs) therapy is a potentially effective treatment option, especially after specific genetic modifications and when used in combination with biomimetic biological scaffolds. In this study, tussah silk fibroin (TSF) scaffolds with interconnected nanofibrous structures were fabricated using a top-down method. We constructed the apelin-overexpressing NSCs that were cocultured with a TSF nanofiber scaffold (TSFNS) that simulated the extracellular matrix in vitro. To verify the therapeutic efficacy of engineered NSCs in vivo, we constructed TBI models and randomized the C57BL/6 mice into three groups: a control group, an NSC-ctrl group (transplantation of NSCs integrated on TSFNS), and an NSC-apelin group (transplantation of apelin-overexpressing NSCs integrated on TSFNS). The neurological functions of the model mice were evaluated in stages. Specimens were obtained 24 days after transplantation for immunohistochemistry, immunofluorescence, and western blot experiments, and statistical analysis was performed. The results showed that the combination of the TSFNS and apelin overexpression guided extension and elevated the proliferation and differentiation of NSCs both in vivo and in vitro. Moreover, the transplantation of TSFNS-NSCs-Apelin reduced lesion volume, enhanced angiogenesis, inhibited neuronal apoptosis, reduced blood-brain barrier damage, and mitigated neuroinflammation. In summary, TSFNS-NSC-Apelin therapy could build a microenvironment that is more conducive to neural repair to promote the recovery of injured neurological function.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":"32 17-18","pages":"539-553"},"PeriodicalIF":4.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10209723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Etv5a Suppresses Neural Progenitor Cell Proliferation by Inhibiting sox2 Transcription. Etv5a通过抑制sox2转录抑制神经祖细胞增殖
IF 4 3区 医学
Stem cells and development Pub Date : 2023-09-01 DOI: 10.1089/scd.2023.0005
Hung-Yu Shih, Hao-Yuan Chen, Yin-Cheng Huang, Tu-Hsueh Yeh, Yi-Chieh Chen, Yi-Chuan Cheng
{"title":"Etv5a Suppresses Neural Progenitor Cell Proliferation by Inhibiting <i>sox2</i> Transcription.","authors":"Hung-Yu Shih,&nbsp;Hao-Yuan Chen,&nbsp;Yin-Cheng Huang,&nbsp;Tu-Hsueh Yeh,&nbsp;Yi-Chieh Chen,&nbsp;Yi-Chuan Cheng","doi":"10.1089/scd.2023.0005","DOIUrl":"https://doi.org/10.1089/scd.2023.0005","url":null,"abstract":"<p><p>Neural progenitor cells are self-renewable, proliferative, and multipotent cell populations that generate diverse types of neurons and glia to build the nervous system. Transcription factors play critical roles in regulating various cellular processes; however, the transcription factors that regulate the development of neural progenitors are yet to be identified. In the present study, we demonstrated that zebrafish <i>etv5a</i> is expressed in the neural progenitor cells of the neuroectoderm. Downregulation of endogenous Etv5a function by <i>etv5a</i> morpholino or an <i>etv5a</i> dominant-negative variant increased the proliferation of <i>sox2</i>-positive neural progenitor cells, accompanied by inhibition of neurogenesis and gliogenesis. These phenotypes in Etv5a-depleted embryos could be rescued by a co-injection with <i>etv5a</i> cRNA. Etv5a overexpression reduced <i>sox2</i> expression. Direct binding of Etv5a to the regulatory elements of <i>sox2</i> was affirmed by chromatin immunoprecipitation. These data revealed that Etv5a directly suppressed <i>sox2</i> expression to reduce the proliferation of neural progenitor cells. In addition, the expression of <i>foxm1</i>, a putative target gene of Etv5a and a direct upstream transcription factor of <i>sox2</i>, was upregulated in Etv5a-deficient embryos. Moreover, the suppression of Foxm1 function by the <i>foxm1</i> dominant-negative construct nullified the phenotype of upregulated <i>sox2</i> expression caused by Etv5a deficiency. Overall, our results indicated that Etv5a regulates the expression of <i>sox2</i> via direct binding to the <i>sox2</i> promoter and indirect regulation by inhibiting <i>foxm1</i> expression. Hence, we revealed the role of Etv5a in the transcriptional hierarchy that regulates the proliferation of neural progenitor cells.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":"32 17-18","pages":"524-538"},"PeriodicalIF":4.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10206825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Role of Macrophage Phenotype in the Vascularization of Prevascularized Human Bone Marrow Mesenchymal Stem Cell Sheets. 巨噬细胞表型在预血管化人骨髓间充质干细胞片血管化中的作用。
IF 4 3区 医学
Stem cells and development Pub Date : 2023-08-01 DOI: 10.1089/scd.2022.0268
Rui Chen, Siqi Long, Lina Ren, Sen Xu, Xiaoning Liu, Jiamin Shi, Jiaxin Liu, Dongyang Ma, Ping Zhou, Liling Ren
{"title":"The Role of Macrophage Phenotype in the Vascularization of Prevascularized Human Bone Marrow Mesenchymal Stem Cell Sheets.","authors":"Rui Chen,&nbsp;Siqi Long,&nbsp;Lina Ren,&nbsp;Sen Xu,&nbsp;Xiaoning Liu,&nbsp;Jiamin Shi,&nbsp;Jiaxin Liu,&nbsp;Dongyang Ma,&nbsp;Ping Zhou,&nbsp;Liling Ren","doi":"10.1089/scd.2022.0268","DOIUrl":"https://doi.org/10.1089/scd.2022.0268","url":null,"abstract":"<p><p>With the development of tissue engineering and regenerative medicine, prevascularized bone marrow mesenchymal stem cell (BMSC) sheets have been regarded as a promising method for tissue regeneration. Furthermore, the inflammatory response is one of the main regulators of vascularization and the restoration of engineered tissue function; among them, macrophages and cytokines produced by them are considered to be the decisive factors of the downstream outcomes. This study investigated the effect of macrophages on the formation of microvascular-like structures of human umbilical vein endothelial cells (HUVECs) in BMSC sheets. First, a human monocytic leukemia cell line (THP-1 cells) was differentiated into derived macrophages (M0) with phorbol 12-myristate 13-acetate and further activated into proinflammatory macrophages (M1 macrophages) with interferon-γ and lipopolysaccharide or anti-inflammatory macrophages (M2 macrophages) with interleukin-4. Then, HUVECs and prevascularized sheets were treated with conditioned media (CM) from different macrophages, and the impact of macrophage phenotypes on vascularized network formation in prevascularized cell sheets was examined by hematoxylin and eosin staining, CD31 immunofluorescence staining and enzyme-linked immunosorbent assay. Our study showed that macrophages may guide the arrangement of endothelial cells through a paracrine pathway. Cell sheets that were cultured in the CM from M2 macrophages were thinner than those cultured in other media. At various time points, the levels of tumor necrosis factor alpha and vascular endothelial growth factor in prevascularized sheets cultured with CM(M1) was higher than that in sheets cultured with other media; however, the levels of platelet-derived growth factor in prevascularized sheets cultured with CM(M2) was higher than that in sheets cultured with other media. These findings suggest that the paracrine effect of macrophages can influence the formation of microvascular networks in prevascularized sheets by regulating the arrangement of cells, the thickness of the cell sheet and the secretion of cytokines related to angiogenesis. Macrophages with different phenotypes have unique effects on prevascularized sheets.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":"32 15-16","pages":"504-514"},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10341287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deletion of p66Shc Dysregulates ERK and STAT3 Activity in Mouse Embryonic Stem Cells, Enhancing Their Naive-Like Self-Renewal in the Presence of Leukemia Inhibitory Factor. p66Shc缺失会失调小鼠胚胎干细胞中ERK和STAT3的活性,增强它们在白血病抑制因子存在下的幼稚样自我更新。
IF 4 3区 医学
Stem cells and development Pub Date : 2023-08-01 DOI: 10.1089/scd.2022.0283
Andrew Powell, Nicole A Edwards, Hailey L M Hunter, Patti Kaiser, Andrew John Watson, Robert Cumming, Dean Harvey Betts
{"title":"Deletion of <i>p66Shc</i> Dysregulates ERK and STAT3 Activity in Mouse Embryonic Stem Cells, Enhancing Their Naive-Like Self-Renewal in the Presence of Leukemia Inhibitory Factor.","authors":"Andrew Powell,&nbsp;Nicole A Edwards,&nbsp;Hailey L M Hunter,&nbsp;Patti Kaiser,&nbsp;Andrew John Watson,&nbsp;Robert Cumming,&nbsp;Dean Harvey Betts","doi":"10.1089/scd.2022.0283","DOIUrl":"https://doi.org/10.1089/scd.2022.0283","url":null,"abstract":"<p><p>The ShcA adapter protein is necessary for early embryonic development. The role of ShcA in development is primarily attributed to its 52 and 46 kDa isoforms that transduce receptor tyrosine kinase signaling through the extracellular signal regulated kinase (ERK). During embryogenesis, ERK acts as the primary signaling effector, driving fate acquisition and germ layer specification. P66Shc, the largest of the ShcA isoforms, has been observed to antagonize ERK in several contexts; however, its role during embryonic development remains poorly understood. We hypothesized that p66Shc could act as a negative regulator of ERK activity during embryonic development, antagonizing early lineage commitment. To explore the role of p66Shc in stem cell self-renewal and differentiation, we created a <i>p66Shc</i> knockout murine embryonic stem cell (mESC) line. Deletion of <i>p66Shc</i> enhanced basal ERK activity, but surprisingly, instead of inducing mESC differentiation, loss of p66Shc enhanced the expression of core and naive pluripotency markers. Using pharmacologic inhibitors to interrogate potential signaling mechanisms, we discovered that p66Shc deletion permits the self-renewal of naive mESCs in the absence of conventional growth factors, by increasing their responsiveness to leukemia inhibitory factor (LIF). We discovered that loss of p66Shc enhanced not only increased ERK phosphorylation but also increased phosphorylation of Signal transducer and activator of transcription in mESCs, which may be acting to stabilize their naive-like identity, desensitizing them to ERK-mediated differentiation cues. These findings identify p66Shc as a regulator of both LIF-mediated ESC pluripotency and of signaling cascades that initiate postimplantation embryonic development and ESC commitment.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":"32 15-16","pages":"434-449"},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9960524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rosalind Franklin Society Proudly Announces the 2022 Award Recipient for Stem Cells and Development. 罗莎琳德·富兰克林协会自豪地宣布2022年干细胞和发展奖获得者。
IF 4 3区 医学
Stem cells and development Pub Date : 2023-08-01 DOI: 10.1089/scd.2023.29014.rfs2022
Gordana Vunjak-Novakovic
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