STEM CELLS最新文献

{"title":"Single-cell transcriptome sequencing in synovial joint: insights of new progenitors and targets in joint development and disease.","authors":"Ziqian Wang, Xianni Yang, Haopeng Yu, Songsong Zhu, Ruiye Bi","doi":"10.1093/stmcls/sxaf008","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf008","url":null,"abstract":"<p><p>Synovial joints, such as knee, temporomandibular, and spinal joints, play a key role in human movement and postural maintenance. Biological research has focused on understanding their developmental process and disease mechanisms. In recent years, the rapid development of single-cell transcriptome sequencing has provided a powerful tool for revealing the mysteries of synovial joints. Single-cell transcriptome sequencing can accurately capture the gene expression profile of each cell, thereby revealing the heterogeneity and interactions of different cell types in synovial joints. During joint development, this technique contributes to elucidating the molecular mechanisms of joint formation, cartilage differentiation, and synovial tissue construction. In terms of joint disease research, single-cell sequencing technology has been applied to the molecular pathology studies of various joint diseases such as osteoarthritis, rheumatoid arthritis, and intervertebral disk degeneration, providing new perspectives and strategies for early diagnosis, accurate treatment, and prognosis assessment of diseases.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Raman Spectroscopies for Cancer Research and Clinical Applications: a Focus on Cancer Stem Cells.","authors":"Francesca Pagliari, Luca Tirinato, Enzo Di Fabrizio","doi":"10.1093/stmcls/sxae084","DOIUrl":"https://doi.org/10.1093/stmcls/sxae084","url":null,"abstract":"<p><p>Over the last two decades, research has increasingly focused on Cancer Stem Cells (CSCs), considered responsible for tumor formation, resistance to therapies, and relapse. The traditional \"static\" CSC model used to describe tumor heterogeneity has been challenged by the evidence of CSC dynamic nature and plasticity. A comprehensive understanding of the mechanisms underlying this plasticity, and the capacity to unambiguously identify cancer markers to precisely target CSCs are crucial aspects for advancing cancer research and introducing more effective treatment strategies. In this context, Raman spectroscopy (RS) and specific Raman schemes, including CARS, SRS, SERS, have emerged as innovative tools for molecular analyses both in vitro and in vivo. In fact, these techniques have demonstrated considerable potential in the field of cancer detection, as well as in intraoperative settings, thanks to their label-free nature and minimal invasiveness. However, the RS integration in pre-clinical and clinical applications, particularly in the CSC field, remains limited. This review provides a concise overview of the historical development of RS and its advantages. Then, after introducing the CSC features and the challenges in targeting them with traditional methods, we review and discuss the current literature about the application of RS for revealing and characterizing CSCs and their inherent plasticity, including a brief paragraph about the integration of artificial intelligence with RS. By providing the possibility to better characterize the cellular diversity in their microenvironment, RS could revolutionize current diagnostic and therapeutic approaches, enabling early identification of CSCs and facilitating the development of personalized treatment strategies.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The miR-290 and miR-302 clusters are essential for reprogramming of fibroblasts to induced pluripotent stem cells.","authors":"Julia Ye, Ryan M Boileau, Ronald J Parchem, Robert L Judson-Torres, Robert Blelloch","doi":"10.1093/stmcls/sxae080","DOIUrl":"10.1093/stmcls/sxae080","url":null,"abstract":"<p><p>The miR-290 and miR-302 clusters of microRNAs are highly expressed in naïve and primed pluripotent stem cells, respectively. Ectopic expression of the embryonic stem cell (ESC)-specific cell cycle regulating family of microRNAs arising from these two clusters dramatically enhances the reprogramming of both mouse and human somatic cells to induced pluripotency. Here, we used genetic knockouts to dissect the requirement for the miR-290 and miR-302 clusters during the reprogramming of mouse fibroblasts into induced pluripotent stem cells (iPSCs) with retrovirally introduced Oct4, Sox2, and Klf4. Knockout of either cluster alone did not negatively impact the efficiency of reprogramming. Resulting cells appeared identical to their ESC microRNA cluster knockout counterparts. In contrast, the combined loss of both clusters blocked the formation of iPSCs. While rare double knockout clones could be isolated, they showed a dramatically reduced proliferation rate, a persistent inability to fully silence the exogenously introduced pluripotency factors, and a transcriptome distinct from individual miR-290 or miR-302 mutant ESC and iPSCs. Taken together, our data show that miR-290 and miR-302 are essential yet interchangeable in reprogramming to the induced pluripotent state.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":"43 2","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes released from immature neurons regulate adult neural stem cell differentiation through microRNA-7a-5p.","authors":"Xiujian Sun, Yexiang Chen, Ying Zhang, Tiantian Cheng, Huisheng Peng, Yanting Sun, Jing-Gen Liu, Chi Xu","doi":"10.1093/stmcls/sxae082","DOIUrl":"10.1093/stmcls/sxae082","url":null,"abstract":"<p><p>Exosomes in the hippocampal dentate gyrus are essential for modulating the cell signaling and controlling the neural differentiation of hippocampal neural stem cells (NSCs), which may determine the level of hippocampal adult neurogenesis. In the present study, we found that exosomes secreted by immature neurons may promote the neuronal differentiation of mouse NSCs in vitro. By miRNA sequencing, we discovered that miR-7a-5p was significantly lower in exosomes from differentiated immature neurons than those from undifferentiated NSCs. By modulating the level of miR-7a-5p, the mimic and inhibitor of miR-7a-5p could either inhibit or promote the neuronal differentiation of NSCs, respectively. Moreover, we confirmed that miR-7a-5p affected neurogenesis by directly targeting Tcf12, a transcription factor responsible for the differentiation of NSCs. The siRNA of Tcf12 inhibited neuronal differentiation of NSCs, while overexpression of Tcf12 promoted NSC differentiation. Thus, we conclude that the miR-7a-5p content in neural exosomes is essential to the fate determination of adult hippocampal neurogenesis and that miR-7a-5p directly targets Tcf12 to regulate adult hippocampal neurogenesis.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of stem cell-derived extracellular vesicles in neurodegenerative diseases associated with cognitive decline.","authors":"Matteo Spinelli, Salvatore Fusco, Claudio Grassi","doi":"10.1093/stmcls/sxae074","DOIUrl":"10.1093/stmcls/sxae074","url":null,"abstract":"<p><p>In the central nervous system, cell-to-cell interaction is essential for brain plassticity and repair, and its alteration is critically involved in the development of neurodegenerative diseases. Neural stem cells are a plentiful source of biological signals promoting neuroplasticity and the maintenance of cognitive functions. Extracellular vesicles (EVs) represent an additional strategy for cells to release signals in the surrounding cellular environment or to exchange information among both neighboring and distant cells. In the last years, rising attention has been devoted to the ability of stem cell (SC)-derived EVs to counteract inflammatory and degenerative brain disorders taking advantage of their immunomodulatory capacities and regenerative potential. Here, we review the role of adult neurogenesis impairment in the cognitive decline associated with neurodegenerative diseases and describe the beneficial effects of SC-derived EVs on brain plasticity and repair also discussing the advantages of SC-derived EV administration vs SC transplantation in the treatment of neurodegenerative disorders.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Notch inhibition enhances morphological reprogramming of microRNA-induced human neurons.","authors":"Kyle F Burbach, Shanyun Wu, Andrew S Yoo","doi":"10.1093/stmcls/sxae079","DOIUrl":"10.1093/stmcls/sxae079","url":null,"abstract":"<p><p>The role of Notch signaling in direct neuronal reprogramming remains unknown despite its importance to brain development in vivo. Here, we use microRNA-induced neurons that are directly reprogrammed from human fibroblasts to determine how Notch signaling contributes to neuronal identity. We found that Notch inhibition during the first week of reprogramming was both necessary and sufficient to enhance neurite outgrowth at a later timepoint, indicating an important role in the erasure of the original cell identity. Accordingly, transcriptomic analysis showed that the effect of Notch inhibition was likely due to improvements in fibroblast fate erasure and silencing of non-neuronal genes. To this effect, we identify MYLIP, whose downregulation in response to Notch inhibition significantly promoted neurite outgrowth. Moreover, Notch inhibition resulted in cells with neuronal transcriptome signatures defined by expressing long genes at a faster rate than the control, demonstrating the effect of accelerated fate erasure on neuronal fate acquisition. Our results demonstrate the antagonistic role of Notch signaling to the pro-neuronal microRNAs 9 and 124 and the benefits of its inhibition to the acquisition of neuronal morphology.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The chondrogenic potential of the bovine tendon sheath-a novel source of stem cells for cartilage repair.","authors":"Ernst B Hunziker, Naomi Nishii, Nahoko Shintani, Kurt Lippuner, Marius J B Keel, Esther Voegelin","doi":"10.1093/stmcls/sxae071","DOIUrl":"10.1093/stmcls/sxae071","url":null,"abstract":"<p><p>The human hand is traumatized more frequently than any other bodily part. Trauma and pathological processes (eg, rheumatoid arthritis, osteoarthritis) commonly implicate the finger joints and specifically damage also the layer of articular cartilage. Endeavors are now being made to surgically repair such cartilage lesions biologically using tissue-engineering approaches that draw on donor cells and/or donor tissues. The tendon sheaths, particularly their inner layers, that is, the peritendineum, surround the numerous tendons in the hand. The peritendineum is composed of mesenchymal tissue. We hypothesize that this tissue harbors pluripotent mesenchymal stem cells and thus could be used for cartilage repair, irrespective of the donor's age. Using a bovine model (young calves vs adult cows), the pluripotentiality of the peritendineal stem cells, namely, their osteogenicity, chondrogenicity, and adipogenicity, was investigated by implementing conventional techniques. Subsequently, the chondrogenic potential of the peritendineal tissue itself was analyzed. Its differentiation into cartilage was induced by the application of specific growth factors (members of the TGF-β-superfamily). The characteristics of the tissue formed were evaluated structurally (immuno) histochemically, histomorphometrically, and biochemically (gene expression and protein level). Our data confirm that the bovine peritendineum contains stem cells whose pluripotentiality is independent of donor age. This tissue could also be induced to differentiate into cartilage, likewise, irrespective of the donor's age. Preliminary investigations with adult human peritendineal biopsy material derived from the hand's peritendineal flexor tendon sheaths revealed that this tissue can also be induced to differentiate into cartilage.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid disease progression of myelodysplastic syndrome is reflected in transcriptomic and functional abnormalities of bone marrow mesenchymal stromal cells.","authors":"Hein Than, Xiubo Fan, Alice M S Cheung, William Y K Hwang, Zhiyong Poon","doi":"10.1093/stmcls/sxae073","DOIUrl":"10.1093/stmcls/sxae073","url":null,"abstract":"<p><p>Bone marrow (BM) mesenchymal stromal cells (MSCs) are important regulators of hematopoietic stem and progenitor cells (HSPCs). When transformed into a dysplastic phenotype, MSCs contribute to hematopoietic diseases such as myelodysplastic syndromes (MDS), but it remains unclear if there are specific properties in MDS-MSCs that contribute to the disease course. To understand this, we investigated MDS-MSCs from fast (MDSfast) vs slow (MDSslow) progressing disease groups and discovered differences between these groups. MDSfast-MSCs secrete more inflammatory factors, support myeloid-skewed differentiation of HSPCs, and importantly, show poorer response to hypomethylation as a key differentiator in GSEA analysis. When exposed to long-term in vivo stimulation with primary MDSfast-MSCs-based scaffolds, healthy donor (HD) HSPCs show elevated NF-κB expression, similar to leukemic HSPCs in MDS. Those \"MDSfast-MSCs-primed\" HD-HSPCs continue to show enhanced engraftment rates in secondary MDS-MSC-based scaffolds, providing evidence for the microenvironmental selection pressures in MDS toward leukemic HSPCs. Together, our data point toward a degree of co-development between MSCs and HSPCs during the progression of MDS, where changes in MDS-MSCs take place mainly at the transcriptomic and functional levels. These unique differences in MDS-MSCs can be utilized to improve disease prognostication and implement targeted therapy for unmet clinical needs.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A small molecule K-3 promotes PDX1 expression and potentiates the differentiation of pluripotent stem cells into insulin-producing pancreatic β cells.","authors":"Tatsuya Yano, Yukihiro Shimaya, Takayuki Enomoto, Toshihiro Kiho, Satoshi Komoriya, Ryutaro Nakashima, Nobuaki Shiraki, Shoen Kume","doi":"10.1093/stmcls/sxae075","DOIUrl":"10.1093/stmcls/sxae075","url":null,"abstract":"<p><p>Insulin-producing pancreatic β-like cells derived from human pluripotent stem cells (PSCs) are anticipated as a novel cell source for cell replacement therapy for patients with diabetes. Here, we describe the identification of small molecule compounds that promote the differentiation of the PSCs into insulin-producing cells by high throughput screening with a chemical library composed of 55 000 compounds. The initial hit compound K-1 and one derivative K-3 increased the proportion of PSC-derived insulin-positive endocrine cells and their glucose-stimulated insulin secretory (GSIS) functions. K-3 preferentially acts on stage 3 pancreatic progenitor cells and increases the population expressing high levels of PDX1. As a result, the ratios of the PSC-derived PDX1/NKX6.1 double-positive endocrine progenitor and INS/NKX6.1 double-positive mono-hormonal endocrine cells were increased. K-3 enhances the expression of functional pancreatic β cell markers and affects biological processes concerning organ development. K-3 also increased the yield of endocrine cells at the end of stage 5. The novel compound is a beneficial new tool for efficiently generating PSC-derived insulin-producing cells with high functionality and differentiation efficiency.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trained mesenchymal stromal cell-based therapy HXB-319 for treating diffuse alveolar hemorrhage in a pristane-induced murine model.","authors":"Hulya Bukulmez, Adrienne T Dennis, Jane Reese-Koc, Scott F Sieg, Brian Clagett, Sarah Kleinsorge-Block, Rodrigo Somoza-Palacios, Nora Singer, Mark Chance, Kristin B Highland, Steven N Emancipator","doi":"10.1093/stmcls/sxae078","DOIUrl":"10.1093/stmcls/sxae078","url":null,"abstract":"<p><strong>Introduction: </strong>Mesenchymal stromal cells (MSCs) can modulate immune responses and suppress inflammation in autoimmune diseases. Although their safety has been established in clinical trials, the efficacy of MSCs is inconsistent due to variability in potency among different preparations and limited specificity in targeting mechanisms driving autoimmune diseases.</p><p><strong>Methods: </strong>We utilized high-dimensional design of experiments methodology to identify factor combinations that modulate gene expression by MSCs to mitigate inflammation. This led to a novel MSC-based cell therapy, HXB-319. Its anti-inflammatory properties were validated in vitro by flow cytometry, RT-PCR, and mass spectrophotometry. To evaluate in vivo efficacy, we treated a diffuse alveolar hemorrhage (DAH) mouse model (C57Bl/6). Seven days post-DAH induction with pristane, mice received either MSCs or HXB-319 (2X106 cells, IP). On day 14, peritoneal lavage fluid (PLF) and lung tissue were collected for flow cytometry, histopathological examination, and mRNA.</p><p><strong>Results: </strong>HXB-319 increased gene expression levels of anti-inflammatory, angiogenic, and anti-fibrotic factors (eg, TSG-6, VEGF, and HGF). KEGG pathway analysis confirmed significant activation of relevant anti-inflammatory, angiogenic, and anti-fibrotic proteins, corroborating RT-PCR results. In the DAH model, HXB-319 significantly reduced lung inflammation and alveolar hemorrhage compared to MSC-treated and untreated DAH mice. HXB-319 treatment also significantly decreased neutrophils, plasmacytoid dendritic cells, and RORγT cells, increased FoxP3+ cells in PLF, and reversed alterations in mRNA encoding IL-6, IL-10, and TSG-6 in lung tissue compared to DAH mice.</p><p><strong>Conclusion: </strong>HXB-319 effectively controls inflammation and prevents tissue damage in pristine-induced DAH, highlighting its therapeutic potential for autoimmune inflammatory diseases.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}