IF 3.6 2区医学

STEM CELLS Pub Date : 2025-10-16 DOI: 10.1093/stmcls/sxaf060

Xiaorui Wang, Ping Yue, Dongming Liu, Xinrui Wen, Xiehua Zhang, Bo Sun, Yi Luo, Liwei Chen, Weidong Li, Hong Liu, Yuchao He, Zhongsheng Tong, Hua Guo

{"title":"PNO1 served as a potential biomarker to promote the stemness and progression of breast cancer via the NF-κB signaling pathway.","authors":"Xiaorui Wang, Ping Yue, Dongming Liu, Xinrui Wen, Xiehua Zhang, Bo Sun, Yi Luo, Liwei Chen, Weidong Li, Hong Liu, Yuchao He, Zhongsheng Tong, Hua Guo","doi":"10.1093/stmcls/sxaf060","DOIUrl":"10.1093/stmcls/sxaf060","url":null,"abstract":"Background: Breast cancer is a highly heterogeneous disease with diverse phenotypes. At present, increasing evidence supports the role of ribosomal biogenesis in human diseases and tumorigenesis. PNO1, as a ribosome assembly factor, plays a key role in the biological synthesis of ribosomes and ribosomal protein mutations associated with human diseases and tumor development. This study explored PNO1's role as a prognostic biomarker for breast cancer.Methods: Clinical samples and online datasets were used to determine PNO1 expression in breast cancers with different molecular phenotypes and clinicopathological subtypes. CCK-8 assays, colony formation assays, wound healing, and transwell assays were performed to investigate tumor cell proliferation, migration, and invasion. Western blot, flow cytometry, and sphere-formation assays were used to assess the effect of PNO1 on breast cancer stemness. RNA-sequencing analysis was also performed to elucidate the underlying mechanism.Results: Results showed that the expression level of PNO1 was upregulated in breast cancer samples. In addition, high PNO1 expression was positively correlated with poor survival in breast cancer patients with different molecular types. Moreover, PNO1 was associated with breast cancer heterogeneity by promoting its stem-like properties both in vitro and in vivo through the NF-κB signaling pathway, which can be suppressed by JSH-23.Conclusions: Our study found that PNO1 expression was positively correlated with poor survival in different molecular subtypes of breast cancer and that PNO1 promoted stem-like properties of breast cancer by activating NF-κB activity. Collectively, PNO1 is a potential prognostic biomarker that plays an important role in breast cancer progression.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090868","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}

引用次数: 0

Human cortical neurons rapidly generated by embryonic stem cell programming integrate into the stroke-injured rat cortex. 胚胎干细胞编程快速生成的人类皮层神经元整合到中风损伤的大鼠皮层。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-10-16 DOI: 10.1093/stmcls/sxaf049

Raquel Martinez-Curiel, Mazin Hajy, Oleg Tsupykov, Linda Jansson, Natalia Avaliani, Juliane Tampé, Emanuela Monni, Galyna Skibo, Olle Lindvall, Sara Palma-Tortosa, Zaal Kokaia

{"title":"Human cortical neurons rapidly generated by embryonic stem cell programming integrate into the stroke-injured rat cortex.","authors":"Raquel Martinez-Curiel, Mazin Hajy, Oleg Tsupykov, Linda Jansson, Natalia Avaliani, Juliane Tampé, Emanuela Monni, Galyna Skibo, Olle Lindvall, Sara Palma-Tortosa, Zaal Kokaia","doi":"10.1093/stmcls/sxaf049","DOIUrl":"10.1093/stmcls/sxaf049","url":null,"abstract":"Stem cell sources capable of producing appropriate cells for replacement will be necessary for functional repair of the injured brain. Here, we have determined whether transcription factor programming of human embryonic stem (hES) cells can be used to generate layer-specific cortical neurons capable of integrating into the stroke-injured rat cortex. Human embryonic stem cells were programmed via overexpression of neurogenin 2 (NGN2). After 7 days, hES-induced neurons (hES-iNs) were characterized in vitro using immunocytochemistry, RT-qPCR, and whole-cell patch-clamp. Cortical ischemic stroke was induced in rats via distal middle cerebral artery occlusion. Forty-eight hours later, hES-iNs were transplanted into the somatosensory cortex adjacent to the ischemic lesion. Three months thereafter, brains were analyzed for expression of neuronal markers, axonal myelination, and synapse formation using immunohistochemistry and immunoelectron microscopy (iEM). Overexpression of NGN2 in hES cells for 7 days generated excitatory neurons, expressing cortical markers at different stages of maturation. After transplantation, the hES-iNs expressed markers of both immature and mature neurons and of upper and deep cortical layers. The hES-iNs sent widespread projections to both hemispheres, and iEM revealed that they were myelinated by host oligodendrocytes and had formed efferent synaptic connections with host cortical neurons. The hES cells programmed via NGN2 overexpression gave rise to subtypes of cortical neurons, capable of integrating structurally into the injured brain, more rapidly than neurons produced by previous protocols. Functional characterization of the grafted hES-iNs and their impact on the balance between brain excitation and inhibition are now highly warranted. This new stem cell source should be considered when, in the future, the most suitable candidate will be selected for clinical translation.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615603","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}

引用次数: 0

Linking mitochondria, fatty acids, and hematopoietic stem cell expansion during infection: implications for aging and metabolic diseases. 在感染期间连接线粒体、脂肪酸和HSC扩张：对衰老和代谢疾病的影响。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-10-16 DOI: 10.1093/stmcls/sxaf053

Katherine Hampton, Alyssa Polski-Delve, Charlotte Hellmich, Stuart A Rushworth

{"title":"Linking mitochondria, fatty acids, and hematopoietic stem cell expansion during infection: implications for aging and metabolic diseases.","authors":"Katherine Hampton, Alyssa Polski-Delve, Charlotte Hellmich, Stuart A Rushworth","doi":"10.1093/stmcls/sxaf053","DOIUrl":"10.1093/stmcls/sxaf053","url":null,"abstract":"In steady state, hematopoietic stem cells (HSCs) reside quiescently in their hypoxic niche with minimal mitochondrial activity, maintaining characteristically low levels of reactive oxygen species (ROS) and instead favoring glycolysis to meet their low energy requirements. However, stress, such as acute infection, triggers a state of emergency hematopoiesis during which HSCs expand more rapidly to produce up to 10-fold more downstream differentiated immune cells. To cope with this demand, HSCs increase their energy production by switching from low ATP-yielding glycolysis to high ATP-yielding mitochondrial oxidative phosphorylation. It is this metabolic switch that enables rapid HSC expansion and differentiation into downstream progeny to increase the immune cell pool and effectively clear the infection. This metabolic switch relies on the sufficient availability of healthy mitochondria as well as fuel in the form of free fatty acids to drive the necessary production of cellular components. This concise review aims to focus on how HSCs increase their mitochondrial content and fuel ATP production via fatty acid oxidation and the impact of HSC dysfunction during aging and other metabolic diseases.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740765","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}

引用次数: 0

Decoding developmental signaling for heart regeneration. 解码心脏再生的发育信号。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-10-13 DOI: 10.1093/stmcls/sxaf066

Thomas W C Knight, Ngefor Asangwe, Sadia Mohsin, Mohsin Khan

{"title":"Decoding developmental signaling for heart regeneration.","authors":"Thomas W C Knight, Ngefor Asangwe, Sadia Mohsin, Mohsin Khan","doi":"10.1093/stmcls/sxaf066","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf066","url":null,"abstract":"The adult heart consists of a fixed number of cardiomyocytes (CMs) determined at birth. CMs once lost due to injury in the adult heart are never replaced, initiating a viscous cycle of adverse events leading to heart failure. Therapeutic interventions that drive cardiac repair by proliferation of the endogenous CMs or adoptive transfer of stem cells such as cardiac tissue derived stem/progenitor cells (CPCs) are promising albeit limited in their ability to repair the heart. Numerous studies have identified an inherent regenerative power of the heart during embryonic and postnatal development. The developmental cardiac tissue can initiate a robust regenerative response leading to complete resolution of injury. Unique cellular and molecular mechanisms in the developmental heart are at the core of this regenerative ability. Upon cardiac maturation, cellular differentiation and changes in molecular signaling hubs active developmentally are 'switched off' in the adult heart. Recent work has shown convincing results for promoting cardiac repair in the adult heart by reactivation of developmental signaling. CPCs engineering with developmental factors or their CMs specific delivery of can reactivate regenerative signaling to augment cardiac structure and function in the adult heart. This review aims to summarize efforts regarding reactivation of developmental signaling factors in the heart using CPCs and CMs. A special emphasis is on embryonic/developmental microRNAs governed signaling pathways for cardiac repair. We provide an in-depth analysis of the current state of the field including discussion of some of the limitations that will be beneficial for future studies. Significance statement: Reactivation of developmental signaling in the heart is promising approach to increase cardiac regeneration after myocardial injury. This article summarizes current state of the field regarding signaling factors that regulated developmental signaling in the context of cardiac progenitor cells and cardiomyocytes to promote cell proliferation and increase their overall repair ability.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278601","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}

引用次数: 0

Novel strategies to expand and engineer hematopoietic stem cells. 扩展和工程造血干细胞的新策略。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-10-09 DOI: 10.1093/stmcls/sxaf065

Bailey R Klein, Angella Blake, Ritisha Rashmil, Amar B Desai

{"title":"Novel strategies to expand and engineer hematopoietic stem cells.","authors":"Bailey R Klein, Angella Blake, Ritisha Rashmil, Amar B Desai","doi":"10.1093/stmcls/sxaf065","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf065","url":null,"abstract":"Hematopoietic stem cell (HSC) transplantation is a lifesaving therapy for hematologic diseases, but its broader application remains constrained by challenges in sourcing, manipulating, and reliably expanding functional HSCs. In this review, we discuss strategies to expand and engineer HSCs by recreating essential aspects of the bone marrow niche. These include defined cytokine cocktails, small molecule modulators, stromal co-culture systems, and biomaterials that promote self-renewal while limiting differentiation. We highlight advances in three-dimensional organoid models and microfluidic platforms that better support long-term repopulating cells and reflect native microenvironments. In parallel, progress in gene delivery platforms, including both viral and nonviral approaches, is enabling more efficient and targeted modification of HSCs for therapeutic use in genetic disorders such as sickle cell disease and β-thalassemia. While these tools have advanced significantly, significant hurdles remain in scaling, preserving stem cell identity, and reducing culture-induced stress. Continued refinement of biomimetic systems and genome engineering technologies will be central to expanding the clinical utility of HSC-based therapies.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249232","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}

引用次数: 0

Unveiling the Gut-Pancreas Axis: Microbial Influence on Stemness and Tumor Microenvironment of PDAC. 揭示肠胰轴：微生物对PDAC干性和肿瘤微环境的影响。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-09-27 DOI: 10.1093/stmcls/sxaf064

Kirtana Arikath, Surinder K Batra, Moorthy P Ponnusamy

引用次数: 0

Comment on "Critical role of the potential O-linked glycosylation sites of CXCR4 in cell migration and bone marrow homing of hematopoietic stem progenitor cells". 评论“CXCR4潜在的o -连锁糖基化位点在造血干细胞祖细胞的细胞迁移和骨髓归巢中的关键作用”。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-09-27 DOI: 10.1093/stmcls/sxaf062

Shan Tao, Dongxue Zhuang, Chengqiang Jin

{"title":"Comment on \"Critical role of the potential O-linked glycosylation sites of CXCR4 in cell migration and bone marrow homing of hematopoietic stem progenitor cells\".","authors":"Shan Tao, Dongxue Zhuang, Chengqiang Jin","doi":"10.1093/stmcls/sxaf062","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf062","url":null,"abstract":"This study by Pan et al. reveals the critical role of O-linked glycosylation at Ser-5 and Ser-9 of mouse CXCR4 in HSPC migration and BM homing. Using CRISPR/Cas9-mediated mutagenesis, in vitro assays, and in vivo models, they show these sites are essential for CXCL12 binding, downstream signaling, and HSPC engraftment. CXCR4[SSA59A] mutants display impaired FAK/MEK/PI3K phosphorylation and reduced homing efficiency without embryonic lethality, offering new insights into CXCR4 glycosylation's structural-functional relationship. The validation across multiple cell types and lectin blot use highlight the methodological rigor. These findings revolutionize chemokine receptor biology understanding and could optimize clinical HSPC transplantation. However, the O-glycosylation characterization is indirect. Future studies using advanced techniques like site-specific O-glycosylation mapping or glycosylation-deficient cell lines could provide more direct evidence. Overall, this work is a significant contribution to glycobiology and stem cell homing mechanisms, setting a high standard for studying receptor post-translational modifications and aligning with STEM CELLS' mission of publishing impactful translational research.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172252","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}

引用次数: 0

Exosomes derived from ADSC suppress endothelial cells ferroptosis and alleviate sepsis acute liver injury via regulation of Keap1/Nrf2/GPX4 axis: an experimental study. ADSC来源的外泌体通过调控Keap1/Nrf2/GPX4轴抑制内皮细胞铁下沉，减轻脓毒症急性肝损伤的实验研究

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-09-27 DOI: 10.1093/stmcls/sxaf063

Xianqi Wang, Dan Wu, Xiaoyang Liu, Yanan Xu, Peiwen Wang, Heliang Fu, Yuexiang Ma, Shanshou Liu, Qianmei Wang, Xian-Jie Xu, Zheng Dai, Qi Zhang, Wen Yin, Kuo Shen, Junjie Li

{"title":"Exosomes derived from ADSC suppress endothelial cells ferroptosis and alleviate sepsis acute liver injury via regulation of Keap1/Nrf2/GPX4 axis: an experimental study.","authors":"Xianqi Wang, Dan Wu, Xiaoyang Liu, Yanan Xu, Peiwen Wang, Heliang Fu, Yuexiang Ma, Shanshou Liu, Qianmei Wang, Xian-Jie Xu, Zheng Dai, Qi Zhang, Wen Yin, Kuo Shen, Junjie Li","doi":"10.1093/stmcls/sxaf063","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf063","url":null,"abstract":"Background: Adipose-derived stem cells exosome (ADSC-exo) has been reported to be effective in alleviating organ dysfunction in sepsis, including acute liver injury (ALI). Whether ADSC-exo protects the liver via suppression of vascular endothelial cell (VEC) ferroptosis is unclear.Methods: We evaluated the viability and migration of VECs and their ferroptosis-related indices. To further elucidate this mechanism, we examined the Nrf2/GPX4 pathway. Cecal ligation and puncture (CLP) was performed to establish a sepsis model to observe the protective effect of ADSC-exo. The death rate and liver tissue injury were observed. We also evaluated inflammation- and ferroptosis-related indices. Next, we examined the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) pathway-related molecules to elucidate the underlying mechanism.Results: ADSC-exo reduced cell injury and ferroptosis in VECs. ADSC-exo increased the expression and nuclear translocation of Nrf2. In the CLP-induced sepsis model, ADSC-exo relieved liver injury and reduced the death rate. Further observations showed that ADSC-exo significantly alleviated oxidative stress injury and ferroptosis in liver tissue, while remarkably increasing the expression of Nrf2 and GPX4.Conclusion: These findings demonstrate the remarkable ability of ADSC-exo to alleviate sepsis-induced ALI by mitigating endothelial cell ferroptosis, providing evidence for the potential clinical application of ADSC-exo in ALI therapy.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172227","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}

引用次数: 0

Resistance to naive and formative pluripotency conversion in RSeT human embryonic stem cells. RSeT人胚胎干细胞对初始和形成性多能转化的抗性。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-09-17 DOI: 10.1093/stmcls/sxaf056

Kevin G Chen, Kory R Johnson, Kyeyoon Park, Dragan Maric, Forest Yang, Wenfang Liu, Yang C Fann, Barbara S Mallon, Pamela G Robey

{"title":"Resistance to naive and formative pluripotency conversion in RSeT human embryonic stem cells.","authors":"Kevin G Chen, Kory R Johnson, Kyeyoon Park, Dragan Maric, Forest Yang, Wenfang Liu, Yang C Fann, Barbara S Mallon, Pamela G Robey","doi":"10.1093/stmcls/sxaf056","DOIUrl":"10.1093/stmcls/sxaf056","url":null,"abstract":"One of the most important properties of human embryonic stem cells (hESCs) is their ability to exist in primed and naive pluripotent states. Our previous meta-analysis indicated the existence of heterogeneous pluripotent states derived from diverse naive protocols. In this study, we characterized a commercial, RSeT-based pluripotent state under various growth conditions. Notably, RSeT hESCs can circumvent the hypoxic growth conditions required by naive hESCs, although some RSeT cells (eg, H1 cells) exhibit much lower single-cell plating efficiency and display altered or significantly retarded cell growth under both normoxia and hypoxia. Importantly, RSeT hPSCs lack many transcriptomic hallmarks of naive and formative pluripotency (the phase between naive and primed states). Integrative transcriptome analysis suggests that our primed and RSeT hESCs are similar to the early stage of post-implantation embryos, in line with previously reported primary hESCs and early hESC cultures. Moreover, RSeT hESCs do not express naive surface markers such as SUSD2 and CD75 at significant levels. At the biochemical level, RSeT hESCs show differential dependence on FGF2 and co-independency on both Janus kinase (JAK) and TGFβ signaling in a cell line-specific manner. Thus, RSeT hESCs represent a previously unrecognized pluripotent state downstream of naive pluripotency. Our data suggest that human naive pluripotent potentials may be restricted in RSeT medium, which sustains FGF2 activity. Hence, this study provides new insights into pluripotent state transitions in vitro.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12471354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937402","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}

引用次数: 0

In reply to the letter to the editor from Jin et al: critical insights into the role of miR-290 and miR-302 clusters in iPSC reprogramming. 在回复Jin等人给编辑的信中：对miR-290和miR-302集群在iPSC重编程中的作用的关键见解。

IF 3.6 2区医学

STEM CELLS Pub Date : 2025-09-17 DOI: 10.1093/stmcls/sxaf046

Robert Blelloch

引用次数: 0

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