Biology OpenPub Date : 2026-09-22DOI: 10.1242/bio.062895
Tenzeela, Muhammad Adnan, Aisha Gul, Sanaullah Khan
{"title":"Ecophysiology and Behavioral Indicators of thermal Stress in Freshwater Crab Himalayapotamon emphyseteum Under Experimental Warming.","authors":"Tenzeela, Muhammad Adnan, Aisha Gul, Sanaullah Khan","doi":"10.1242/bio.062895","DOIUrl":"https://doi.org/10.1242/bio.062895","url":null,"abstract":"<p><p>Global warming poses substantial challenges to ectothermic organisms, which depend on physiological and behavioural adjustments to maintain homeostasis under thermal stress. We examined the effects of experimental warming on oxygen consumption, ammonia excretion, feeding activity, surface activity, burrow retreat, and critical thermal maximum (CTMax) in Himalayapotamon emphyseteum. Crabs were exposed to three independent experimental temperatures (27, 31, and 33°C), and physiological and behavioural responses were assessed. Oxygen consumption rate increased significantly with temperature, from 1.917±0.192 mg O₂ g⁻¹ h⁻¹ at 27°C to 3.606±0.631 at 31°C and 5.835±0.792 at 33°C (p<0.001). Ammonia excretion did not differ between 27 and 31°C but increased significantly at 33°C (p<0.001). Feeding rate and surface activity decreased significantly with increasing temperature, whereas burrow retreat increased significantly (p<0.001). CTMax was strongly affected by heating rate, increasing from 32.90±0.88°C at 1°C min⁻¹ to 34.10±0.74°C at 1°C per 30 min and 35.90±0.32°C at 1°C h⁻¹ (p<0.001). Experimental warming elicited pronounced physiological and behavioural responses, while measured upper thermal limits were strongly influenced by heating rate and experimental protocol.Reduced feeding and surface activity, increased burrow retreat, and elevated metabolic rate indicate significant physiological and behavioral responses to warming.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biology OpenPub Date : 2026-09-15Epub Date: 2026-09-11DOI: 10.1242/bio.062493
Lara Feulner, Florian Wünnemann, Naimeh Rafatian, Jenna Liang, Anaïs Medouni, Philipp Hofmann, Marc-Phillip Hitz, Denis Schapiro, Severine Leclerc, Patrick Piet van Vliet, Gregor Andelfinger
{"title":"Transcriptional dynamics of the murine heart during perinatal development at single-cell resolution.","authors":"Lara Feulner, Florian Wünnemann, Naimeh Rafatian, Jenna Liang, Anaïs Medouni, Philipp Hofmann, Marc-Phillip Hitz, Denis Schapiro, Severine Leclerc, Patrick Piet van Vliet, Gregor Andelfinger","doi":"10.1242/bio.062493","DOIUrl":"10.1242/bio.062493","url":null,"abstract":"<p><p>Heart maturation and remodelling during the foetal and early postnatal period are critical for the proper survival and growth of the foetus, yet our knowledge of the molecular processes involved is lacking for many cardiac cell types. To gain a deeper understanding of the transcriptional dynamics of the heart during the perinatal period, we performed single-cell RNA sequencing on foetal and early postnatal mouse hearts to establish a catalogue of 49,769 single-cell transcriptomes and used this for bioinformatics analyses. Pseudotime analyses and RNAscope fluorescence in situ hybridisation showed that while lncRNA H19 expression decreased over time in multiple cardiac cell types, it remained stably expressed in endocardial and valve endothelial cells. To further investigate this in a human setting, we generated human induced pluripotent stem cell (hiPSC)-derived endothelial cells and used single-cell data to develop a sorting strategy to separate endocardial from vascular endothelial cells, ensuring endothelial subtype purity. Knockdown of H19 in hiPSC-derived endocardial cells resulted in morphological changes, decreased expression of endothelial markers, and increased expression of mesenchymal markers, consistent with the onset of endothelial-to-mesenchymal transition. Together, our data suggest a role for H19 in maintaining endocardial and valve endothelial cell states during perinatal heart maturation.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"15 9","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biology OpenPub Date : 2026-09-15Epub Date: 2026-09-11DOI: 10.1242/bio.062799
Baibhav R Barbaruah, Rahmadani P Airlangga, Hidetaka Ito
{"title":"Heat-responsive ONSEN long terminal repeats integrate heat shock factor motifs, DNA methylation and natural sequence variation in Arabidopsis.","authors":"Baibhav R Barbaruah, Rahmadani P Airlangga, Hidetaka Ito","doi":"10.1242/bio.062799","DOIUrl":"10.1242/bio.062799","url":null,"abstract":"<p><p>ONSEN is a heat-activated Ty1/copia retrotransposon in Arabidopsis thaliana controlled by heat shock factors (HSFs) and epigenetic silencing. Heat shock element (HSE)-like sequences in ONSEN long terminal repeats (LTRs) contribute to heat responsiveness, but relationships among sequence architecture, basal DNA methylation and natural variation remain unclear. We combined transcription-factor motif prediction, transposable-element comparisons, methylome and RNA sequencing (RNA-seq) data, and Arabidopsis genome assemblies. In silico disruption of five HSE cores eliminated HSF-family motif compatibility in the selected design and all 5119 exact-guanine-cytosine (GC) alternatives. Across 16 curated Columbia-0 terminal windows, ONSEN contained 33-49 non-redundant HSF motif-coordinate placements per 800 bp window and was strongly enriched relative to 1930 non-ONSEN transposable elements across score thresholds and continuous metrics. Direct comparison with 779 non-ONSEN LTR retrotransposons showed selectively elevated basal CHH methylation (where H = A, C or T) at ONSEN termini. Genome-wide RNA-seq analysis revealed broad heat-responsive gene and transposable-element changes, including strong ONSEN induction, whereas candidate-window analysis distinguished ONSEN from most HSF-rich non-ONSEN outliers. ONSEN-like variants across eight accessions generally retained HSF-compatible motifs while altering predicted DNA binding with one finger-family motif composition. Together, these findings define ONSEN terminal regions as HSF-rich regulatory sequences that retain heat-responsive potential within a methylated chromatin context and identify candidates for functional analysis.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biology OpenPub Date : 2026-09-15DOI: 10.1242/bio.062526
Madeline Daniel, Frances Parrott, Laura A Voss, Yoona Shim, Trent Nause, Bella Root, Tevere Loeb, Paige A Barta, Greg J Hermann
{"title":"The de novo formation and maintenance of C. elegans lysosome-related organelles.","authors":"Madeline Daniel, Frances Parrott, Laura A Voss, Yoona Shim, Trent Nause, Bella Root, Tevere Loeb, Paige A Barta, Greg J Hermann","doi":"10.1242/bio.062526","DOIUrl":"10.1242/bio.062526","url":null,"abstract":"<p><p>Lysosome-related organelles (LROs) are cell-type-specific organelles derived from the endosomal system. Their lack of ubiquity requires that they be created during cell differentiation. To investigate how LROs are first formed, we characterized the biogenesis of Caenorhabditis elegans gut granules and found that these intestinally restricted LROs are generated de novo during a short period of early embryogenesis. Intriguingly, we found that gut granule number and size remain unchanged throughout the rest of embryonic development. The transition from formation to maintenance coincides with the loss of the GLO-1/Rab32 guanine nucleotide exchange factor (GEF) subunit CCZ-1 from gut granules. Our investigations manipulating the presence and activity of GLO-1/Rab32 reveal that LRO biogenesis remains active during embryogenesis when the steady-state number of gut granules does not change. These studies define a system where the de novo formation of LROs can be investigated and provide insights into the mechanisms maintaining LROs once they have been generated.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"15 9","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biology OpenPub Date : 2026-09-15Epub Date: 2026-09-11DOI: 10.1242/bio.062670
Julie Fleitz, Clémence Furic, Charli S Davies, Jenna Palttala, Valentina Giongo, Loan Hognon, Suvi Ruuskanen, Sophie Reichert
{"title":"Impacts of early-life thermal challenge on development, survival, and physiology in wild great tits.","authors":"Julie Fleitz, Clémence Furic, Charli S Davies, Jenna Palttala, Valentina Giongo, Loan Hognon, Suvi Ruuskanen, Sophie Reichert","doi":"10.1242/bio.062670","DOIUrl":"10.1242/bio.062670","url":null,"abstract":"<p><p>Rapid climate change is increasing thermal extremes that may challenge developing endotherms. In altricial birds, early postnatal life is a sensitive period because thermoregulatory and physiological systems are still maturing. We experimentally manipulated nest temperature in a wild population of great tit to test whether mild, ecologically realistic heat (+2.3°C) and cold (-1.3°C) challenges affected development and physiology. Treatments were applied from days 2-8 post-hatching, and we measured growth, survival, hydration status (plasma osmolarity and uric acid), mitochondrial density, and immunoglobulin levels. Contrary to our predictions, thermal manipulation had no detectable effects on survival, morphology, or physiological traits at either day 8 or day 14. In contrast, all physiological markers varied significantly with age, reflecting normal osmoregulatory, metabolic, and immune development. These findings suggest that moderate, short-term thermal deviations during early development fall within the tolerance range of this population, or that parental behaviour buffered nestlings against temperature changes. However, stronger or prolonged extremes may exceed buffering capacity, and delayed effects cannot be excluded. Long-term studies are needed to assess latent fitness costs under increasingly variable climates.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biology OpenPub Date : 2026-09-15Epub Date: 2026-09-10DOI: 10.1242/bio.062669
Fabienne Dreier, Peter Ditte, Philipp Weiss, Tobias Boothe, Jochen C Rink
{"title":"Multiplexed gene expression analysis in dissociated and intact planarian flatworm tissues using in situ hybridization chain reaction.","authors":"Fabienne Dreier, Peter Ditte, Philipp Weiss, Tobias Boothe, Jochen C Rink","doi":"10.1242/bio.062669","DOIUrl":"10.1242/bio.062669","url":null,"abstract":"<p><p>Planarians are an important model system for studying whole-body regeneration. The visualization of gene expression patterns during this process is an essential experimental technique to understand the underlying mechanisms. Multicolor fluorescence in situ hybridization (FISH) is currently the standard approach for gene expression analysis. However, the small number of available haptens limits probe multiplexing options, and the required sequential development of individual probes can be extremely time consuming. In situ hybridization chain reaction (HCR) is a newer technique that promises parallel hybridization of multiple genes via annealing of fluorescently labeled hairpins to target sequences. While HCR is well established in several model organisms, including mice and Drosophila, existing protocols perform poorly on whole-mount planarians. Here, we report a systematically optimized HCR protocol that is faster and less labor intensive than traditional FISH. This method can be applied to dissociated planarian cells or combined with the established DEEP-Clear method to label whole-mount animals. These improvements establish HCR as a useful addition to the planarian tool kit, particularly for multiplex gene expression analysis.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148719898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biology OpenPub Date : 2026-09-15Epub Date: 2026-09-08DOI: 10.1242/bio.062807
Laura L Baxter, Sarah E Lee, Kevin A Fuentes, Iman A Mosley, Jonathan D Raymond, Faycal Guedj, Di Zhou, Donna K Slonim, Elliot J Glotfelty, David Tweedie, Nigel H Grieg, Diana W Bianchi
{"title":"Fasudil induces anti-inflammatory transcriptomic changes and increased proliferation in human trisomy 21 neural progenitor cells.","authors":"Laura L Baxter, Sarah E Lee, Kevin A Fuentes, Iman A Mosley, Jonathan D Raymond, Faycal Guedj, Di Zhou, Donna K Slonim, Elliot J Glotfelty, David Tweedie, Nigel H Grieg, Diana W Bianchi","doi":"10.1242/bio.062807","DOIUrl":"10.1242/bio.062807","url":null,"abstract":"<p><p>Down syndrome (DS) results from trisomy for human chromosome 21 and is the most frequent genetic cause of intellectual disability. No effective treatments currently exist that improve neurodevelopment and cognition. Atypical brain development in individuals with DS is apparent before birth, which suggests that the optimal time to begin administration of therapies is prenatally. Human neural progenitor cell (NPC) cultures provide a tractable in vitro model system to examine the effects of trisomy 21 (T21) on neurodevelopment and to measure the effects of pharmacological interventions. Here, we report the results of preclinical studies evaluating 24 candidate therapies. RNA sequencing analyses found that euploid and T21 NPCs showed different transcriptomic responses to five candidate pharmacotherapies. The Rho-associated coiled-coil kinase inhibitor fasudil increased proliferation of T21 NPCs, reduced expression of inflammatory pathway genes in T21 NPCs, and reduced markers of inflammation in LPS-stimulated microglial model systems. These results demonstrate that fasudil can alter multiple T21-associated abnormalities in a beneficial manner, suggesting that fasudil warrants further study as a candidate prenatal pharmacotherapy for DS.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biology OpenPub Date : 2026-09-15Epub Date: 2026-09-01DOI: 10.1242/bio.062573
Neil A Youngson, Susan M Corley, Kyoko Hasebe, Aynaz Tajaddini, Michael D Kendig, Margaret J Morris
{"title":"Maternal obesity in rats results in male-specific increases in genome-wide DNA methylation in postnatal offspring liver.","authors":"Neil A Youngson, Susan M Corley, Kyoko Hasebe, Aynaz Tajaddini, Michael D Kendig, Margaret J Morris","doi":"10.1242/bio.062573","DOIUrl":"10.1242/bio.062573","url":null,"abstract":"<p><p>Male-specific peripubertal DNA demethylation in the liver has been reported in mice. Here, we investigated whether it also occurs in rats, the influence of maternal obesity and whether DNA demethylation changes contribute to observed sex-specific effects of maternal obesity in offspring. Female rats were fed a high-fat, high-sugar 'cafeteria' (Caf) diet before mating with standard chow-fed males. The offspring liver methylome and transcriptome were examined. Body weight was higher in Caf-fed dams prior to mating, during gestation and at parturition. Male and female offspring from Caf-fed dams had lower birth weights but higher adult weights and adiposity than offspring from chow-fed dams. A comparison of DNA methylation in 3-week-old weaner males versus female siblings from chow-fed dams did not reveal the male-specific DNA demethylation that was previously reported in mice. However, strong maternal diet effects in male weaner offspring methylation were observed. A comparison of female weaners from chow- versus Caf-fed dams showed a range of differences, with 39% of differentially methylated regions (DMRs) having higher methylation in Caf offspring and 61% of DMRs having higher methylation in chow offspring. In stark contrast, 99% of maternal-diet-induced DMRs in male weaner offspring had higher methylation in offspring from Caf-fed dams. This suggests that maternal obesity induces widespread hypermethylation in the male offspring liver at weaning. However, a comparison with RNA sequencing data revealed limited transcriptional changes at this developmental stage or in adult offspring. While these data highlight how environmentally sensitive DNA methylation is in the male rodent perinatal period, these methylation changes may not be a major contributor to sex differences in developmentally programmed liver disease.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biology OpenPub Date : 2026-09-15Epub Date: 2026-09-17DOI: 10.1242/bio.062837
Naser Alshamsi, Francisca Rojo-Cortés, Jervis Fernandes, Callum Perrett, Bangfu Zhu, Samaher Fahy, Guiyi Li, Anna Lassota, Marta Moreira, Alicia Hidalgo
{"title":"The neurotrophin DNT-2 via the Toll-2 receptor regulates neuronal survival and morphology during visual system development.","authors":"Naser Alshamsi, Francisca Rojo-Cortés, Jervis Fernandes, Callum Perrett, Bangfu Zhu, Samaher Fahy, Guiyi Li, Anna Lassota, Marta Moreira, Alicia Hidalgo","doi":"10.1242/bio.062837","DOIUrl":"10.1242/bio.062837","url":null,"abstract":"<p><p>During vertebrate nervous system development, neurons are produced in excess, and those receiving neurotrophin ligands are maintained, enabling neural circuit establishment. An apoptotic wave sweeps across the Drosophila pupal visual system, but whether neurotrophins participate in forming adult visual circuits remains unknown. Here, we show that Drosophila neurotrophin-3 (spz-3) and DNT-2 (spz-5) are expressed in retinal cells and medulla neurons and Toll receptors across the visual system. Using loss- and gain-of-function conditions for DNT-3 (spz-3) and DNT-2 (spz-5), we show that they both can, and are required to, promote cell survival. Importantly, genetic interaction data show that DNT-2 can function together with Toll-2. DNT-2 neurons were identified as medulla Mi1 neurons that connect to lamina L1 neurons expressing Toll-2. Loss of function for DNT-2 or Toll-2 induced apoptosis, and Toll-2 knock-down prevented the pro-survival function of DNT-2. DNT-2 overexpression resulted in excess Toll-2 neurons, whereas most Toll-2 neurons were lost in DNT-2 mutants. Furthermore, DNT-2 and Toll-2 were required for appropriate L1 axonal columnar organisation and dendritic morphology. Altogether, evolutionarily conserved neurotrophin family ligands control neuronal number through Toll receptors during visual circuit development in Drosophila.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biology OpenPub Date : 2026-09-15Epub Date: 2026-09-18DOI: 10.1242/bio.062801
Madalena Vaz Santos, Bauke V Schomakers, Marta Llobet Ayala, Tara Jamali, Michel van Weeghel, Ans M M van Pelt, Callista L Mulder, Geert Hamer
{"title":"Characterization of the metabolome and proteome of stem cell-derived human primordial germ cell-like cells: a multi-omics approach.","authors":"Madalena Vaz Santos, Bauke V Schomakers, Marta Llobet Ayala, Tara Jamali, Michel van Weeghel, Ans M M van Pelt, Callista L Mulder, Geert Hamer","doi":"10.1242/bio.062801","DOIUrl":"10.1242/bio.062801","url":null,"abstract":"<p><p>Primordial germ cells (PGCs) are the population of cells that, in the human embryo, are initially specified at day 12 post-fertilization and form the precursor cells for future gametes. Although in vitro differentiation of PGCs from human stem cells has been achieved, these human PGC-like cells (hPGCLCs) fail to completely mature without the use of ex vivo human or animal gonadal soma. Previous studies in mice revealed that several metabolic changes occur during the specification and maturation of these cells, which are essential for their developmental progress. However, little is known about the metabolic profile of human PGCs. Due to the scarcity of human PGCs, particularly at the early specification stage, hPGCLCs serve as a research model to study PGC formation. To characterize the metabolic and proteomic profile of these cells, we differentiated hPGCLCs using induced pluripotent stem cells and performed a mass spectrometry analysis to establish their metabolome and proteome. These cells revealed a distinct metabolic profile, with changes particularly evident at the proteome level. This included a shift between canonical and noncanonical citric acid cycles in hPGCLCs, downregulation of late-stage glycolysis and reduction of nucleotide de novo synthesis. By providing an integrative map of these metabolic networks, we aim to provide insight into the metabolism of hPGCLC development that could help improve methods for fully in vitro differentiation and maturation of hPGCLCs.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}