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Linking citation and retraction data reveals the demographics of scientific retractions among highly cited authors.
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-01-30 eCollection Date: 2025-01-01 DOI: 10.1371/journal.pbio.3002999
John P A Ioannidis, Angelo Maria Pezzullo, Antonio Cristiano, Stefania Boccia, Jeroen Baas
{"title":"Linking citation and retraction data reveals the demographics of scientific retractions among highly cited authors.","authors":"John P A Ioannidis, Angelo Maria Pezzullo, Antonio Cristiano, Stefania Boccia, Jeroen Baas","doi":"10.1371/journal.pbio.3002999","DOIUrl":"10.1371/journal.pbio.3002999","url":null,"abstract":"<p><p>Retractions are becoming increasingly common but still account for a small minority of published papers. It would be useful to generate databases where the presence of retractions can be linked to impact metrics of each scientist. We have thus incorporated retraction data in an updated Scopus-based database of highly cited scientists (top 2% in each scientific subfield according to a composite citation indicator). Using data from the Retraction Watch database (RWDB), retraction records were linked to Scopus citation data. Of 55,237 items in RWDB as of August 15, 2024, we excluded non-retractions, retractions clearly not due to any author error, retractions where the paper had been republished, and items not linkable to Scopus records. Eventually, 39,468 eligible retractions were linked to Scopus. Among 217,097 top-cited scientists in career-long impact and 223,152 in single recent year (2023) impact, 7,083 (3.3%) and 8,747 (4.0%), respectively, had at least 1 retraction. Scientists with retracted publications had younger publication age, higher self-citation rates, and larger publication volume than those without any retracted publications. Retractions were more common in the life sciences and rare or nonexistent in several other disciplines. In several developing countries, very high proportions of top-cited scientists had retractions (highest in Senegal (66.7%), Ecuador (28.6%), and Pakistan (27.8%) in career-long citation impact lists). Variability in retraction rates across fields and countries suggests differences in research practices, scrutiny, and ease of retraction. Addition of retraction data enhances the granularity of top-cited scientists' profiles, aiding in responsible research evaluation. However, caution is needed when interpreting retractions, as they do not always signify misconduct; further analysis on a case-by-case basis is essential. The database should hopefully provide a resource for meta-research and deeper insights into scientific practices.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002999"},"PeriodicalIF":9.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Oxygen-binding proteins aid oxygen diffusion to enhance fitness of a yeast model of multicellularity.
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-01-30 eCollection Date: 2025-01-01 DOI: 10.1371/journal.pbio.3002975
Whitney Wong, Pablo Bravo, Peter J Yunker, William C Ratcliff, Anthony J Burnetti
{"title":"Oxygen-binding proteins aid oxygen diffusion to enhance fitness of a yeast model of multicellularity.","authors":"Whitney Wong, Pablo Bravo, Peter J Yunker, William C Ratcliff, Anthony J Burnetti","doi":"10.1371/journal.pbio.3002975","DOIUrl":"10.1371/journal.pbio.3002975","url":null,"abstract":"<p><p>Oxygen availability is a key factor in the evolution of multicellularity, as larger and more sophisticated organisms often require mechanisms allowing efficient oxygen delivery to their tissues. One such mechanism is the presence of oxygen-binding proteins, such as globins and hemerythrins, which arose in the ancestor of bilaterian animals. Despite their importance, the precise mechanisms by which oxygen-binding proteins influenced the early stages of multicellular evolution under varying environmental oxygen levels are not yet clear. We address this knowledge gap by heterologously expressing the oxygen-binding proteins myoglobin and myohemerythrin in snowflake yeast, a model system of simple, undifferentiated multicellularity. These proteins increased the depth and rate of oxygen diffusion, increasing the fitness of snowflake yeast growing aerobically. Experiments show that, paradoxically, oxygen-binding proteins confer a greater fitness benefit for larger organisms when O2 is least limiting. We show via biophysical modeling that this is because facilitated diffusion is more efficient when oxygen is abundant, transporting a greater quantity of O2 which can be used for metabolism. By alleviating anatomical diffusion limitations to oxygen consumption, the evolution of oxygen-binding proteins in the oxygen-rich Neoproterozoic may have been a key breakthrough enabling the evolution of increasingly large, complex multicellular metazoan lineages.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002975"},"PeriodicalIF":9.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Interaction of cardiac leiomodin with the native cardiac thin filament.
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-01-30 eCollection Date: 2025-01-01 DOI: 10.1371/journal.pbio.3003027
Madison Little, Cristina M Risi, Tania M Larrinaga, Mason D Summers, Tyler Nguyen, Garry E Smith, Jennifer Atherton, Carol C Gregorio, Alla S Kostyukova, Vitold E Galkin
{"title":"Interaction of cardiac leiomodin with the native cardiac thin filament.","authors":"Madison Little, Cristina M Risi, Tania M Larrinaga, Mason D Summers, Tyler Nguyen, Garry E Smith, Jennifer Atherton, Carol C Gregorio, Alla S Kostyukova, Vitold E Galkin","doi":"10.1371/journal.pbio.3003027","DOIUrl":"10.1371/journal.pbio.3003027","url":null,"abstract":"<p><p>Every heartbeat depends on cyclical contraction-relaxation produced by the interactions between myosin-containing thick and actin-based thin filaments (TFs) arranged into a crystalline-like lattice in the cardiac sarcomere. Therefore, the maintenance of thin filament length is crucial for myocardium function. The thin filament is comprised of an actin backbone, the regulatory troponin complex and tropomyosin that controls interactions between thick and thin filaments. Thin filament length is controlled by the tropomodulin family of proteins; tropomodulin caps pointed ends of thin filaments, and leiomodin (Lmod) promotes elongation of thin filaments by a \"leaky-cap\" mechanism. The broader distribution of Lmod on the thin filament implied to the possibility of its interaction with the sides of thin filaments. Here, we use biochemical and structural approaches to show that cardiac Lmod (Lmod2) binds to a specific region on the native cardiac thin filament in a Ca2+-dependent manner. We demonstrate that Lmod2's unique C-terminal extension is required for binding to the thin filament actin backbone and suggest that interactions with the troponin complex assist Lmod2's localization on the surface of thin filaments. We propose that Lmod2 regulates the length of cardiac thin filaments in a working myocardium by protecting newly formed thin filament units during systole and promoting actin polymerization at thin filament pointed ends during diastole.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3003027"},"PeriodicalIF":9.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11813103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Pilin antigenic variants impact gonococcal lifestyle and antibiotic tolerance by modulating interbacterial forces.
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-01-30 eCollection Date: 2025-01-01 DOI: 10.1371/journal.pbio.3003022
Isabelle Wielert, Sebastian Kraus-Römer, Thorsten E Volkmann, Lisa Craig, Paul G Higgins, Berenike Maier
{"title":"Pilin antigenic variants impact gonococcal lifestyle and antibiotic tolerance by modulating interbacterial forces.","authors":"Isabelle Wielert, Sebastian Kraus-Römer, Thorsten E Volkmann, Lisa Craig, Paul G Higgins, Berenike Maier","doi":"10.1371/journal.pbio.3003022","DOIUrl":"10.1371/journal.pbio.3003022","url":null,"abstract":"<p><p>Type 4 pili (T4P) are multifunctional filaments involved in adhesion, surface motility, biofilm formation, and horizontal gene transfer. These extracellular polymers are surface-exposed and, therefore, act as antigens. The human pathogen Neisseria gonorrhoeae uses pilin antigenic variation to escape immune surveillance, yet it is unclear how antigenic variation impacts most other functions of T4P. Here, we addressed this question by replacing the major pilin of a laboratory strain with pilins from clinical isolates. We reveal that the resulting strains vary substantially in their attractive forces. Strongly interacting bacteria form microcolonies while weakly interacting bacteria retain a planktonic lifestyle. In mixed microcolonies, different variant strains segregate in agreement with the differential strength of adhesion hypothesis. By combining structural predictions and laser tweezers experiments, we show that the C-terminal region of the pilin is crucial for attraction. Lifestyle affects growth kinetics and antibiotic tolerance. In the presence of ceftriaxone or ciprofloxacin, the killing kinetics indicate strongly increased tolerance of aggregating strains. We propose that pilin antigenic variation produces a mixed population containing variants optimized for growth, colonization, or survivability under external stress. Different environments select different variants, ensuring the survival and reproduction of the population as a whole.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3003022"},"PeriodicalIF":9.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11813099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Insect size responses to climate change vary across elevations according to seasonal timing.
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-01-30 eCollection Date: 2025-01-01 DOI: 10.1371/journal.pbio.3002805
César R Nufio, Monica M Sheffer, Julia M Smith, Michael T Troutman, Simran J Bawa, Ebony D Taylor, Sean D Schoville, Caroline M Williams, Lauren B Buckley
{"title":"Insect size responses to climate change vary across elevations according to seasonal timing.","authors":"César R Nufio, Monica M Sheffer, Julia M Smith, Michael T Troutman, Simran J Bawa, Ebony D Taylor, Sean D Schoville, Caroline M Williams, Lauren B Buckley","doi":"10.1371/journal.pbio.3002805","DOIUrl":"10.1371/journal.pbio.3002805","url":null,"abstract":"<p><p>Body size declines are a common response to warming via both plasticity and evolution, but variable size responses have been observed for terrestrial ectotherms. We investigate how temperature-dependent development and growth rates in ectothermic organisms induce variation in size responses. Leveraging long-term data for six montane grasshopper species spanning 1,768-3 901 m, we detect size shifts since ~1960 that depend on elevation and species' seasonal timing. Size shifts have been concentrated at low elevations, with the early emerging species (those that overwinter as juveniles) increasing in size, while later season species are becoming smaller. Interannual temperature variation accounts for the size shifts. The earliest season species may be able to take advantage of warmer conditions accelerating growth during early spring development, whereas warm temperatures may adversely impact later season species via mechanisms such as increased rates of energy use or thermal stress. Grasshoppers tend to capitalize on warm conditions by both getting bigger and reaching adulthood earlier. Our analysis further reinforces the need to move beyond expectations of universal responses to climate change to consider how environmental exposure and sensitivity vary across elevations and life histories.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002805"},"PeriodicalIF":9.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
morphoHeart: A quantitative tool for integrated 3D morphometric analyses of heart and ECM during embryonic development.
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-01-29 eCollection Date: 2025-01-01 DOI: 10.1371/journal.pbio.3002995
Juliana Sánchez-Posada, Christopher J Derrick, Emily S Noël
{"title":"morphoHeart: A quantitative tool for integrated 3D morphometric analyses of heart and ECM during embryonic development.","authors":"Juliana Sánchez-Posada, Christopher J Derrick, Emily S Noël","doi":"10.1371/journal.pbio.3002995","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002995","url":null,"abstract":"<p><p>Heart development involves the complex structural remodelling of a linear heart tube into an asymmetrically looped and ballooned organ. Previous studies have associated regional expansion of extracellular matrix (ECM) space with tissue morphogenesis during development. We have developed morphoHeart, a 3D tissue segmentation and morphometry software with a user-friendly graphical interface (GUI) that delivers the first integrated 3D visualisation and multiparametric analysis of both heart and ECM morphology in live embryos. morphoHeart reveals that the ECM undergoes regional dynamic expansion and reduction during cardiac development, concomitant with chamber-specific morphological maturation. We use morphoHeart to demonstrate that regionalised ECM expansion driven by the ECM crosslinker Hapln1a promotes atrial lumen expansion during heart development. Finally, morphoHeart's GUI expands its use beyond that of cardiac tissue, allowing its segmentation and morphometric analysis tools to be applied to z-stack images of any fluorescently labelled tissue.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002995"},"PeriodicalIF":9.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11778784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 ubiquitin-conjugating enzyme UBE2D maintains a youthful proteome and ensures protein quality control during aging by sustaining proteasome activity.
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-01-29 eCollection Date: 2025-01-01 DOI: 10.1371/journal.pbio.3002998
Liam C Hunt, Michelle Curley, Kudzai Nyamkondiwa, Anna Stephan, Jianqin Jiao, Kanisha Kavdia, Vishwajeeth R Pagala, Junmin Peng, Fabio Demontis
{"title":"The ubiquitin-conjugating enzyme UBE2D maintains a youthful proteome and ensures protein quality control during aging by sustaining proteasome activity.","authors":"Liam C Hunt, Michelle Curley, Kudzai Nyamkondiwa, Anna Stephan, Jianqin Jiao, Kanisha Kavdia, Vishwajeeth R Pagala, Junmin Peng, Fabio Demontis","doi":"10.1371/journal.pbio.3002998","DOIUrl":"10.1371/journal.pbio.3002998","url":null,"abstract":"<p><p>Ubiquitin-conjugating enzymes (E2s) are key for protein turnover and quality control via ubiquitination. Some E2s also physically interact with the proteasome, but it remains undetermined which E2s maintain proteostasis during aging. Here, we find that E2s have diverse roles in handling a model aggregation-prone protein (huntingtin-polyQ) in the Drosophila retina: while some E2s mediate aggregate assembly, UBE2D/effete (eff) and other E2s are required for huntingtin-polyQ degradation. UBE2D/eff is key for proteostasis also in skeletal muscle: eff protein levels decline with aging, and muscle-specific eff knockdown causes an accelerated buildup in insoluble poly-ubiquitinated proteins (which progressively accumulate with aging) and shortens lifespan. Mechanistically, UBE2D/eff is necessary to maintain optimal proteasome function: UBE2D/eff knockdown reduces the proteolytic activity of the proteasome, and this is rescued by transgenic expression of human UBE2D2, an eff homolog. Likewise, human UBE2D2 partially rescues the lifespan and proteostasis deficits caused by muscle-specific effRNAi and re-establishes the physiological levels of effRNAi-regulated proteins. Interestingly, UBE2D/eff knockdown in young age reproduces part of the proteomic changes that normally occur in old muscles, suggesting that the decrease in UBE2D/eff protein levels that occurs with aging contributes to reshaping the composition of the muscle proteome. However, some of the proteins that are concertedly up-regulated by aging and effRNAi are proteostasis regulators (e.g., chaperones and Pomp) that are transcriptionally induced presumably as part of an adaptive stress response to the loss of proteostasis. Altogether, these findings indicate that UBE2D/eff is a key E2 ubiquitin-conjugating enzyme that ensures protein quality control and helps maintain a youthful proteome composition during aging.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002998"},"PeriodicalIF":9.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11778781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Decreased SynMuv B gene activity in response to viral infection leads to activation of the antiviral RNAi pathway in C. elegans.
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-01-29 eCollection Date: 2025-01-01 DOI: 10.1371/journal.pbio.3002748
Ashwin Seetharaman, Himani Galagali, Elizabeth Linarte, Mona H X Liu, Jennifer D Cohen, Kashish Chetal, Ruslan Sadreyev, Alex J Tate, Taiowa A Montgomery, Gary Ruvkun
{"title":"Decreased SynMuv B gene activity in response to viral infection leads to activation of the antiviral RNAi pathway in C. elegans.","authors":"Ashwin Seetharaman, Himani Galagali, Elizabeth Linarte, Mona H X Liu, Jennifer D Cohen, Kashish Chetal, Ruslan Sadreyev, Alex J Tate, Taiowa A Montgomery, Gary Ruvkun","doi":"10.1371/journal.pbio.3002748","DOIUrl":"10.1371/journal.pbio.3002748","url":null,"abstract":"<p><p>RNA interference (RNAi) mediates antiviral defense in many eukaryotes. Caenorhabditis elegans mutants that disable RNAi are more sensitive to viral infection. Many mutants that enhance RNAi have also been identified; these mutations may reveal genes that are normally down-regulated in antiviral defense. About one-third of the score of mutants that enhance RNAi are in synMuv B genes, identified 30 years ago in unrelated screens for increased growth factor signaling. Many synMuv B genes encode dREAM complex chromatin-regulatory proteins found in nearly all animals and plants. We show that mRNAs which are highly induced in synMuv B mutants are congruent with those induced by Orsay RNA virus infection, suggesting that the enhanced RNAi of synMuv B mutants may also be triggered by down-regulation of synMuvB gene activity in an Orsay virus infection of wild type. The multivulval (Muv) phenotype of synMuv B mutants requires the presence of a second nematode-specific synMuv A gene mutation, but the enhanced RNAi of synMuv B mutants does not require a second synMuv A mutation. To test if Orsay viral infection down-regulates synMuv B gene activity, we infected a single synMuv A mutant with Orsay virus and found that a Muv phenotype could be induced. Thus, decreased synMuv B gene activity is part of the normal C. elegans viral defense response. In support of the model that decreased syn- Muv B gene activity enhances antiviral response, we found that synMuv B mutants have 50 to 100× lower viral RNA levels during an Orsay virus infection than wild type. Thus down-regulation of synMuv B activity to enhance RNAi is a key component in the defense response to viral infection. Small RNA deep sequencing analysis of dREAM complex mutants revealed siRNA profiles indicative of such a response. Thus, the pan-eukaryotic synMuv B genes constitute an element in C. elegans antiviral defense which is conserved across many eukaryotes where it also may act in viral defense. The enhanced RNAi and conservation of the dREAM complex mutants suggests new therapeutic avenues to boost antiviral defenses.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002748"},"PeriodicalIF":9.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11778786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Lineage tracing studies suggest that the placenta is not a de novo source of hematopoietic stem cells.
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-01-28 eCollection Date: 2025-01-01 DOI: 10.1371/journal.pbio.3003003
Xiaowen Chen, Joanna Tober, Martin Dominguez, Alan T Tang, Jenna Bockman, Jisheng Yang, Sneha Mani, Chin Nien Lee, Mei Chen, Triloshan Thillaikumaran, Patricia Mericko-Ishizuka, Monica Mainigi, Nancy A Speck, Mark L Kahn
{"title":"Lineage tracing studies suggest that the placenta is not a de novo source of hematopoietic stem cells.","authors":"Xiaowen Chen, Joanna Tober, Martin Dominguez, Alan T Tang, Jenna Bockman, Jisheng Yang, Sneha Mani, Chin Nien Lee, Mei Chen, Triloshan Thillaikumaran, Patricia Mericko-Ishizuka, Monica Mainigi, Nancy A Speck, Mark L Kahn","doi":"10.1371/journal.pbio.3003003","DOIUrl":"10.1371/journal.pbio.3003003","url":null,"abstract":"<p><p>Definitive hematopoietic stem and progenitor cells (HSPCs) arise from a small number of hemogenic endothelial cells (HECs) within the developing embryo. Understanding the origin and ontogeny of HSPCs is of considerable interest and potential therapeutic value. It has been proposed that the murine placenta contains HECs that differentiate into HSPCs. However, during human gestation HSPCs arise in the aorta considerably earlier than when they can first be detected in the placenta, suggesting that the placenta may primarily serve as a niche. We found that the Runx1 transcription factor, which is required to generate HSPCs from HECs, is not expressed by mouse placental ECs. To definitively determine whether the mouse placenta is a site of HSPC emergence, we performed lineage tracing experiments with a Hoxa13Cre allele that specifically labels ECs in the placenta and umbilical cord (UC), but not in the yolk sac or embryo. Immunostaining revealed Hoxa13Cre lineage-traced HECs and HSPCs in the UC, a known site of HECs, but not the placenta. Consistent with these findings, ECs harvested from the E10.5 aorta and UC, but not the placenta, gave rise to hematopoietic cells ex vivo, while colony forming assays using E14.5 fetal liver revealed only 2% of HSPCs arose from Hoxa13-expressing precursors. In contrast, the pan-EC Cdh5-CreERT2 allele labeled most HSPCs in the mouse placenta. Lastly, we found that RUNX1 and other HEC genes were not expressed in first-trimester human placenta villous ECs, suggesting that human placenta is not hemogenic. Our findings demonstrate that the placenta functions as a site for expansion of HSPCs that arise within the embryo proper and is not a primary site of HSPC emergence.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3003003"},"PeriodicalIF":9.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 neurohormone tyramine stimulates the secretion of an insulin-like peptide from the Caenorhabditis elegans intestine to modulate the systemic stress response.
IF 9.8 1区 生物学
PLoS Biology Pub Date : 2025-01-28 eCollection Date: 2025-01-01 DOI: 10.1371/journal.pbio.3002997
Tania Veuthey, Jeremy T Florman, Sebastián Giunti, Stefano Romussi, María José De Rosa, Mark J Alkema, Diego Rayes
{"title":"The neurohormone tyramine stimulates the secretion of an insulin-like peptide from the Caenorhabditis elegans intestine to modulate the systemic stress response.","authors":"Tania Veuthey, Jeremy T Florman, Sebastián Giunti, Stefano Romussi, María José De Rosa, Mark J Alkema, Diego Rayes","doi":"10.1371/journal.pbio.3002997","DOIUrl":"10.1371/journal.pbio.3002997","url":null,"abstract":"<p><p>The DAF-2/insulin/insulin-like growth factor signaling (IIS) pathway plays an evolutionarily conserved role in regulating reproductive development, life span, and stress resistance. In Caenorhabditis elegans, DAF-2/IIS signaling is modulated by an extensive array of insulin-like peptides (ILPs) with diverse spatial and temporal expression patterns. However, the release dynamics and specific functions of these ILPs in adapting to different environmental conditions remain poorly understood. Here, we show that the ILP, insulin-3 (INS-3), plays a crucial role in modulating the response to various environmental stressors in C. elegans. ins-3 mutants display increased resistance to heat, oxidative stress, and starvation; however, this advantage is countered by slower reproductive development under favorable conditions. We find that ins-3 expression is downregulated in response to environmental stressors, whereas, the neurohormone tyramine, which is released during the acute flight response, increases ins-3 expression. We show that tyramine induces intestinal calcium (Ca2+) transients through the activation of the TYRA-3 receptor. Our data support a model in which tyramine negatively impacts environmental stress resistance by stimulating the release of INS-3 from the intestine via the activation of a TYRA-3-Gαq-IP3 pathway. The release of INS-3 systemically activates the DAF-2 pathway, resulting in the inhibition of cytoprotective mechanisms mediated by DAF-16/FOXO. These studies offer mechanistic insights into a brain-gut communication pathway that weighs adaptive strategies to respond to acute and long-term stressors.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002997"},"PeriodicalIF":9.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
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