Life Science Alliance最新文献_第9页

Structure and dynamics of 2x(CENP-A/H4)₂ octasome reveal a possible intermediate in centromeric chromatin. 2x(CENP-A/H4)2八体的结构和动力学揭示了着丝粒染色质中可能的中间体。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-12-15 Print Date: 2026-03-01 DOI: 10.26508/lsa.202503377

Ahmad Ali-Ahmad, Mira Mors, Manuel Carrer, Xinmeng Li, Silvija Bilokapić, Mario Halić, Michele Cascella, Nikolina Sekulić

引用次数: 0

A step-by-step guide to performing cancer metabolism research using custom-made media. 使用定制媒体进行癌症代谢研究的分步指南。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-12-10 Print Date: 2026-02-01 DOI: 10.26508/lsa.202503529

Sophie Seifert, Francisco Yanqui-Rivera, Tim Kühn, Lena Elise Høyland, Toman Borteçen, Bella Agranovich, Lara Elea Eckhardt, Martin Herdt, Alessa Henneberg, Verena Panitz, Faisal Hayat, Marie Migaud, Gernot Poschet, Ifat Abramovich, Eyal Gottlieb, Jeroen Krijgsveld, Mathias Ziegler, Mirja Tamara Prentzell, Christiane A Opitz

{"title":"A step-by-step guide to performing cancer metabolism research using custom-made media.","authors":"Sophie Seifert, Francisco Yanqui-Rivera, Tim Kühn, Lena Elise Høyland, Toman Borteçen, Bella Agranovich, Lara Elea Eckhardt, Martin Herdt, Alessa Henneberg, Verena Panitz, Faisal Hayat, Marie Migaud, Gernot Poschet, Ifat Abramovich, Eyal Gottlieb, Jeroen Krijgsveld, Mathias Ziegler, Mirja Tamara Prentzell, Christiane A Opitz","doi":"10.26508/lsa.202503529","DOIUrl":"10.26508/lsa.202503529","url":null,"abstract":"The preparation of custom-made media offers precise control over nutrient composition, enabling detailed studies of cellular metabolism. We demonstrate how self-made media formulations enable diverse assay designs and readouts to assess cancer metabolism. Self-made media can be used in Seahorse assays to measure mitochondrial respiration under defined conditions. In nutrient deprivation experiments, amino acid or vitamin removal can uncover how cancer cells adapt to metabolic stress. Using labeled amino acids enables analysis of nascent protein synthesis and translational regulation, while stable-isotope tracing reveals metabolic fluxes through key pathways. This guide presents a suite of metabolic assays using custom-made media, covering experimental design, the selection of controls, sample preparation, data acquisition, and interpretation. The accompanying online media calculator \"Media Minds\" streamlines the creation of custom media formulations, ensuring accuracy and reproducibility.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12696398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145724387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Loss of Y chromosome in Alzheimer's patients co-occurs with somatic mutations beyond CHIP drivers. 阿尔茨海默病患者的Y染色体缺失与CHIP驱动因素以外的体细胞突变共同发生。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-12-10 Print Date: 2026-02-01 DOI: 10.26508/lsa.202503533

Edyta Rychlicka-Buniowska, Daniil Sarkisyan, Monika Horbacz, Bożena Bruhn-Olszewska, Kinga Drężek-Chyła, Mikołaj Koszyński, Hanna Davies, Ulana Juhas, Magdalena Wójcik-Zalewska, Alicja Klich-Rączka, Lena Kilander, Martin Ingelsson, Karolina Bukowska-Strakova, Kazimierz Węglarczyk, Maciej Siedlar, Jarosław Baran, Janusz Ryś, Arkadiusz Piotrowski, Natalia Filipowicz, Jan P Dumanski

{"title":"Loss of Y chromosome in Alzheimer's patients co-occurs with somatic mutations beyond CHIP drivers.","authors":"Edyta Rychlicka-Buniowska, Daniil Sarkisyan, Monika Horbacz, Bożena Bruhn-Olszewska, Kinga Drężek-Chyła, Mikołaj Koszyński, Hanna Davies, Ulana Juhas, Magdalena Wójcik-Zalewska, Alicja Klich-Rączka, Lena Kilander, Martin Ingelsson, Karolina Bukowska-Strakova, Kazimierz Węglarczyk, Maciej Siedlar, Jarosław Baran, Janusz Ryś, Arkadiusz Piotrowski, Natalia Filipowicz, Jan P Dumanski","doi":"10.26508/lsa.202503533","DOIUrl":"10.26508/lsa.202503533","url":null,"abstract":"Loss of Y chromosome (LOY) and clonal hematopoiesis of indeterminate potential (CHIP) are common age-related events with implications for aging and Alzheimer disease (AD). LOY is linked to increased AD risk, whereas CHIP may be protective, and their co-occurrence remains unclear. We conducted whole-exome sequencing of CD4+ T cells, NK cells, and myeloid cells from AD patients and controls exhibiting LOY or retention of Y chromosome. We identified 39 variants in known myeloid and lymphoid driver genes, with up to 35% co-occurring with LOY in the same clone. In addition, we detected 192 unknown drivers of clonal hematopoiesis, enriched in AD-LOY individuals (odds ratio 4.8, P = 0.041). In myeloid cells, total driver burden correlated with LOY (ρ = 0.52, P = 0.00041). These results indicate that LOY is a primary driver of clonal hematopoiesis in AD, seeding myeloid clones that accumulate unknown driver variants, whereas most canonical CHIP mutations arise independently. Our study reveals distinct, partially overlapping clonal architectures for LOY and CHIP and highlights LOY-driven myeloid expansion as a contributor to AD pathogenesis.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12696397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145724335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Conserved 3D genome reorganization during DNA repair. DNA修复过程中保守的三维基因组重组。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-12-03 Print Date: 2026-02-01 DOI: 10.26508/lsa.202503498

Veysel Oğulcan Kaya, Ogün Adebali, Hanspeter Naegeli, Michelle N Yancoskie

{"title":"Conserved 3D genome reorganization during DNA repair.","authors":"Veysel Oğulcan Kaya, Ogün Adebali, Hanspeter Naegeli, Michelle N Yancoskie","doi":"10.26508/lsa.202503498","DOIUrl":"10.26508/lsa.202503498","url":null,"abstract":"The mammalian genome is hierarchically structured to maintain accessibility and flexibility for essential nuclear processes such as transcription and DNA repair. A recent study using high-throughput 3D genome mapping reveals that nucleotide excision repair triggers large-scale chromatin rearrangements, reinforcing topologically associating domains and chromatin compartments. Notably, similar principles of chromatin stabilization are observed during double-strand break repair, consistent with the notion that chromatin restructuring may be an active and conserved DNA repair strategy rather than a passive consequence of damage. The observed stabilization is postulated to optimize repair efficiency by reducing the search space for damage, enhancing DNA accessibility at damage sites, increasing local concentrations of repair factors, and preventing aberrant chromosomal rearrangements. By synthesizing emerging evidence on nucleotide excision repair-driven chromatin dynamics and its parallels with double-strand break repair, this review examines how genome architecture actively shapes the DNA damage response and highlights broader implications for genetic diseases and therapeutic strategies.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12676481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Correction: Transient PU.1 low fetal progenitors generate lymphoid progeny that contribute to adult immunity. 纠正：短暂的PU.1低的胎儿祖细胞产生淋巴样后代，有助于成人免疫。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-12-02 Print Date: 2026-02-01 DOI: 10.26508/lsa.202503567

Encarnacion Montecino-Rodriguez, Oscar I Estrada, Kenneth Dorshkind

引用次数: 0

GPR88 localization to primary cilia in neurons is cell-type specific. GPR88在神经元原代纤毛上的定位具有细胞类型特异性。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-12-02 Print Date: 2026-02-01 DOI: 10.26508/lsa.202503366

Yenni H Li Guan, Brigitte L Kieffer, Mark von Zastrow, Aliza T Ehrlich

{"title":"GPR88 localization to primary cilia in neurons is cell-type specific.","authors":"Yenni H Li Guan, Brigitte L Kieffer, Mark von Zastrow, Aliza T Ehrlich","doi":"10.26508/lsa.202503366","DOIUrl":"10.26508/lsa.202503366","url":null,"abstract":"GPR88 is an orphan G protein-coupled receptor that regulates dopamine neurotransmission and is a target for neuropsychiatric disorders. In addition to the somatic membrane, GPR88 can localize to the primary cilium, a membrane microdomain known for dynamically enriching receptors and signaling molecules. However, the distribution of GPR88 in neuronal primary cilia remains uncharacterized. Here, we characterize GPR88 distribution at primary cilia in two brain areas. We show that in the striatum, GPR88 localizes both to somatodendritic and primary cilia compartments on inhibitory GABAergic medium spiny neurons. In contrast, in the somatosensory cortex, GPR88 localizes to somatodendritic and nuclear compartments and not primary cilia of excitatory spiny stellate neurons. In addition, we found that cilia density and length were similar between Gpr88 knockout and wild-type animals. Together, we provide key evidence for neuronal cell-type specific regulation of GPR88 localization to primary cilia, suggesting neuron subtype specific regulatory mechanisms govern receptor ciliary targeting in the brain.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12672383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

TRPM7 and magnesium orchestrate human CD4 T-cell activation and differentiation. TRPM7和镁协调人CD4 t细胞的活化和分化。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-12-01 Print Date: 2026-02-01 DOI: 10.26508/lsa.202503357

Anna Madlmayr, Kilian Hoelting, Birgit Karner-Hoeger, Dorothea Lewitz, Marius Weng, Severin Hacker, Julia Eder, Katharina Horner, Christine Schedlberger, Tanja Haider, Max Lechner, Michelle Duggan, Rylee Ross, F David Horgen, Markus Sperandio, Alexander Dietrich, Thomas Gudermann, Susanna Zierler

{"title":"TRPM7 and magnesium orchestrate human CD4 T-cell activation and differentiation.","authors":"Anna Madlmayr, Kilian Hoelting, Birgit Karner-Hoeger, Dorothea Lewitz, Marius Weng, Severin Hacker, Julia Eder, Katharina Horner, Christine Schedlberger, Tanja Haider, Max Lechner, Michelle Duggan, Rylee Ross, F David Horgen, Markus Sperandio, Alexander Dietrich, Thomas Gudermann, Susanna Zierler","doi":"10.26508/lsa.202503357","DOIUrl":"10.26508/lsa.202503357","url":null,"abstract":"T-lymphocyte activation is a crucial process in the regulation of innate and adaptive immune responses. The ion channel-kinase TRPM7, transient receptor potential cation channel subfamily M, member 7, has previously been implicated in cellular Mg2+ homeostasis, proliferation, and immune cell modulation. Here, we show that pharmacological and genetic silencing of TRPM7 leads to diminished activation and influences signaling pathways that guide human TH17 or Treg cell differentiation, following TCR-mediated stimulation. In primary human CD4 T cells and CRISPR-Cas9-engineered Jurkat T cells, inactivation or loss of TRPM7 led to distorted Mg2+ homeostasis and Ca2+ signaling, reduced NFAT translocation, decreased IL-2 secretion and altered TH cell differentiation. While the activation of primary human CD4 T cells, as well as in vitro polarization into pro-inflammatory TH17 cells was critically dependent on TRPM7, the polarization of naïve CD4 T cells into FOXP3+ regulatory T cells was not. Taken together, these results highlight TRPM7 as molecular switch in lymphocyte activation and polarization. Thus, suggesting a therapeutic potential for TRPM7 in numerous T-cell mediated diseases.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12670122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

The unfolded protein response in progeria arteries originates from non-endothelial cell types. 早衰动脉中的未折叠蛋白反应来源于非内皮细胞类型。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-12-01 Print Date: 2026-02-01 DOI: 10.26508/lsa.202503485

Raquel A Silva, Fatih Sarigol, G Elif Karagöz, Selma Osmanagic-Myers, Roland Foisner

{"title":"The unfolded protein response in progeria arteries originates from non-endothelial cell types.","authors":"Raquel A Silva, Fatih Sarigol, G Elif Karagöz, Selma Osmanagic-Myers, Roland Foisner","doi":"10.26508/lsa.202503485","DOIUrl":"10.26508/lsa.202503485","url":null,"abstract":"Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disease caused by a mutation in LMNA, leading to the expression of a prelamin A variant called progerin. HGPS hallmarks include accelerated cardiovascular disease and atherosclerosis, caused in part by ER stress-induced apoptosis of vascular smooth muscle cells. As a dysregulated unfolded protein response (UPR) can induce endothelial cell (EC) pathology during aging, we investigated whether loss of proteostasis contributes to EC dysfunction in HGPS, using an endothelium-specific HGPS mouse model. Contrary to previous reports in vascular smooth muscle cells and fibroblasts, we found no robust activation of UPR in ECs constitutively expressing progerin, and cells retained the ability to elicit potent UPR when exposed to external ER stress. Unlike aortic tissue derived from mice with endothelium-specific progerin expression, aorta from Lmna G609G/+ mice with ubiquitous progerin expression showed up-regulation of the UPR, suggesting that the UPR in HGPS aorta is primarily rooted in non-ECs. Analysis of scRNA-Seq datasets from aorta in Lmna G609G/G609G mice confirmed this hypothesis. Our data indicate that UPR activation is a cell-type-specific phenomenon in progerin-expressing arteries.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12670121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

A simple, efficient, and scalable method to generate oocyte-like cells in vitro. 一种在体外产生卵母细胞样细胞的简单、高效和可扩展的方法。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-11-21 Print Date: 2026-02-01 DOI: 10.26508/lsa.202503379

Ami Banno, Kana Mizuno, Mizuki Sakamoto, Sota Komatsubara, Kenjiro Shirane, Katsuhiko Hayashi, Nobuhiko Hamazaki, Koshi Imami, Shigenobu Yonemura, Takashi Ishiuchi

{"title":"A simple, efficient, and scalable method to generate oocyte-like cells in vitro.","authors":"Ami Banno, Kana Mizuno, Mizuki Sakamoto, Sota Komatsubara, Kenjiro Shirane, Katsuhiko Hayashi, Nobuhiko Hamazaki, Koshi Imami, Shigenobu Yonemura, Takashi Ishiuchi","doi":"10.26508/lsa.202503379","DOIUrl":"10.26508/lsa.202503379","url":null,"abstract":"Understanding the molecular basis of oocyte identity and function is essential not only for basic biology but also for clinical applications, as it is closely linked to female infertility. However, technical challenges remain in advancing this understanding, mainly because of the difficulty in obtaining a sufficient number of oocytes. In this study, through refining previously reported three-dimensional protocols, we established a two-dimensional culture method that efficiently generates oocyte-like cells, referred to as mini-oocytes, from mouse embryonic stem cells. This method requires minimal labor, does not rely on supporting somatic cells, and leverages a transcription factor-mediated approach for oocyte-like cell generation. Our transcriptome and proteome analyses revealed significant similarities between in vitro-derived mini-oocytes and in vivo oocytes, despite their relatively smaller size. Furthermore, we demonstrated the utility of mini-oocytes for investigating oocyte-specific molecular features through a small-scale knockout screen targeting the subcortical maternal complex. Given the simplicity, efficiency, and scalability of the mini-oocyte induction method, it offers a practical platform for conducting experiments that are otherwise challenging with in vivo oocytes.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12640779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Identifying space-resolved proteins of the murine thymus, by combining MALDI-MSI and proteomics. 结合MALDI-MSI和蛋白质组学，鉴定小鼠胸腺的空间分辨蛋白。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-11-20 Print Date: 2026-01-01 DOI: 10.26508/lsa.202503205

Jennifer T Aguilan, Carlos Madrid-Aliste, Joshua Fischer, Maria K Lagou, Simone Sidoli, George S Karagiannis

{"title":"Identifying space-resolved proteins of the murine thymus, by combining MALDI-MSI and proteomics.","authors":"Jennifer T Aguilan, Carlos Madrid-Aliste, Joshua Fischer, Maria K Lagou, Simone Sidoli, George S Karagiannis","doi":"10.26508/lsa.202503205","DOIUrl":"10.26508/lsa.202503205","url":null,"abstract":"Identifying spatially resolved proteomes has advanced markedly, yet integrating definitive protein identification with precise spatial localization in a single workflow remains challenging. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) enables antibody-free mapping of proteins in tissue sections, but its capacity for unambiguous identification is limited. Here, we present a combined MALDI-MSI and liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach to map protein localization and track spatial changes in murine thymus during chemotherapy-induced involution and regeneration. Our workflow incorporates a scoring algorithm (pepBridge) that aligns MALDI-MSI molecular signals with LC-MS/MS identifications, enabling confident assignment of proteins, critical to thymic function. Using this pipeline, we reveal spatiotemporal changes in proteins involved in cell migration, cytoskeletal remodeling, and thymic regeneration. Notably, we identify distinct spatial shifts in nucleoprotein TPR and tubulin-associated chaperone A (TBCA), corresponding to chemotherapy-driven architectural remodeling. Translationally, these findings highlight pathways and targets to promote immune recovery in pediatric cancer patients undergoing cytoreductive therapy. Analytically, this framework advances spatial proteomics by enabling high-confidence protein identification in lymphoid tissues, broadening the potential of translational proteomic research.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12634821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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