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Decoding contextual influences on auditory perception from primary auditory cortex.
IF 6.4 1区 生物学
eLife Pub Date : 2024-12-09 DOI: 10.7554/eLife.94296
Bernhard Englitz, Sahar Akram, Mounya Elhilali, Shihab Shamma
{"title":"Decoding contextual influences on auditory perception from primary auditory cortex.","authors":"Bernhard Englitz, Sahar Akram, Mounya Elhilali, Shihab Shamma","doi":"10.7554/eLife.94296","DOIUrl":"10.7554/eLife.94296","url":null,"abstract":"<p><p>Perception can be highly dependent on stimulus context, but whether and how sensory areas encode the context remains uncertain. We used an ambiguous auditory stimulus - a tritone pair - to investigate the neural activity associated with a preceding contextual stimulus that strongly influenced the tritone pair's perception: either as an ascending or a descending step in pitch. We recorded single-unit responses from a population of auditory cortical cells in awake ferrets listening to the tritone pairs preceded by the contextual stimulus. We find that the responses adapt locally to the contextual stimulus, consistent with human MEG recordings from the auditory cortex under the same conditions. Decoding the population responses demonstrates that cells responding to pitch-changes are able to predict well the context-sensitive percept of the tritone pairs. Conversely, decoding the individual pitch representations and taking their distance in the circular Shepard tone space predicts the <i>opposite</i> of the percept. The various percepts can be readily captured and explained by a neural model of cortical activity based on populations of adapting, pitch and pitch-direction cells, aligned with the neurophysiological responses. Together, these decoding and model results suggest that contextual influences on perception may well be already encoded at the level of the primary sensory cortices, reflecting basic neural response properties commonly found in these areas.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799592","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
How vision shapes the paths we choose.
IF 6.4 1区 生物学
eLife Pub Date : 2024-12-09 DOI: 10.7554/eLife.104965
Arthur D Kuo
{"title":"How vision shapes the paths we choose.","authors":"Arthur D Kuo","doi":"10.7554/eLife.104965","DOIUrl":"10.7554/eLife.104965","url":null,"abstract":"<p><p>A mathematical model can predict the path walkers take through a rugged landscape, including the tendency of people to avoid paths that are too steep, even if it means going farther.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799605","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
Pharmacologically inducing regenerative cardiac cells by small molecule drugs. 通过小分子药物诱导再生心脏细胞。
IF 6.4 1区 生物学
eLife Pub Date : 2024-12-09 DOI: 10.7554/eLife.93405
Wei Zhou, Kezhang He, Chiyin Wang, Pengqi Wang, Dan Wang, Bowen Wang, Han Geng, Hong Lian, Tianhua Ma, Yu Nie, Sheng Ding
{"title":"Pharmacologically inducing regenerative cardiac cells by small molecule drugs.","authors":"Wei Zhou, Kezhang He, Chiyin Wang, Pengqi Wang, Dan Wang, Bowen Wang, Han Geng, Hong Lian, Tianhua Ma, Yu Nie, Sheng Ding","doi":"10.7554/eLife.93405","DOIUrl":"10.7554/eLife.93405","url":null,"abstract":"<p><p>Adult mammals, unlike some lower organisms, lack the ability to regenerate damaged hearts through cardiomyocytes (CMs) dedifferentiation into cells with regenerative capacity. Developing conditions to induce such naturally unavailable cells with potential to proliferate and differentiate into CMs, that is, regenerative cardiac cells (RCCs), in mammals will provide new insights and tools for heart regeneration research. In this study, we demonstrate that a two-compound combination, CHIR99021 and A-485 (2C), effectively induces RCCs from human embryonic stem cell-derived TNNT2<sup>+</sup> CMs in vitro, as evidenced by lineage tracing experiments. Functional analysis shows that these RCCs express a broad spectrum of cardiogenesis genes and have the potential to differentiate into functional CMs, endothelial cells, and smooth muscle cells. Importantly, similar results were observed in neonatal rat CMs both in vitro and in vivo. Remarkably, administering 2C in adult mouse hearts significantly enhances survival and improves heart function post-myocardial infarction. Mechanistically, CHIR99021 is crucial for the transcriptional and epigenetic activation of genes essential for RCC development, while A-485 primarily suppresses H3K27Ac and particularly H3K9Ac in CMs. Their synergistic effect enhances these modifications on RCC genes, facilitating the transition from CMs to RCCs. Therefore, our findings demonstrate the feasibility and reveal the mechanisms of pharmacological induction of RCCs from endogenous CMs, which could offer a promising regenerative strategy to repair injured hearts.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799919","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 identification of extensive samples of motor units in human muscles reveals diverse effects of neuromodulatory inputs on the rate coding. 对人体肌肉中大量运动单元样本的鉴定揭示了神经调节输入对速率编码的不同影响。
IF 6.4 1区 生物学
eLife Pub Date : 2024-12-09 DOI: 10.7554/eLife.97085
Simon Avrillon, François Hug, Roger M Enoka, Arnault H D Caillet, Dario Farina
{"title":"The identification of extensive samples of motor units in human muscles reveals diverse effects of neuromodulatory inputs on the rate coding.","authors":"Simon Avrillon, François Hug, Roger M Enoka, Arnault H D Caillet, Dario Farina","doi":"10.7554/eLife.97085","DOIUrl":"10.7554/eLife.97085","url":null,"abstract":"<p><p>Movements are performed by motoneurons transforming synaptic inputs into an activation signal that controls muscle force. The control signal emerges from interactions between ionotropic and neuromodulatory inputs to motoneurons. Critically, these interactions vary across motoneuron pools and differ between muscles. To provide the most comprehensive framework to date of motor unit activity during isometric contractions, we identified the firing activity of extensive samples of motor units in the tibialis anterior (129 ± 44 per participant; n=8) and the vastus lateralis (130 ± 63 per participant; n=8) muscles during isometric contractions of up to 80% of maximal force. From this unique dataset, the rate coding of each motor unit was characterised as the relation between its instantaneous firing rate and the applied force, with the assumption that the linear increase in isometric force reflects a proportional increase in the net synaptic excitatory inputs received by the motoneuron. This relation was characterised with a natural logarithm function that comprised two stages. The initial stage was marked by a steep acceleration of firing rate, which was greater for low- than medium- and high-threshold motor units. The second stage comprised a linear increase in firing rate, which was greater for high- than medium- and low-threshold motor units. Changes in firing rate were largely non-linear during the ramp-up and ramp-down phases of the task, but with significant prolonged firing activity only evident for medium-threshold motor units. Contrary to what is usually assumed, our results demonstrate that the firing rate of each motor unit can follow a large variety of trends with force across the pool. From a neural control perspective, these findings indicate how motor unit pools use gain control to transform inputs with limited bandwidths into an intended muscle force.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799923","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
Cross-species alignment along the chronological axis reveals evolutionary effect on structural development of the human brain.
IF 6.4 1区 生物学
eLife Pub Date : 2024-12-09 DOI: 10.7554/eLife.96020
Yue Li, Qinyao Sun, Shunli Zhu, Congying Chu, Jiaojian Wang
{"title":"Cross-species alignment along the chronological axis reveals evolutionary effect on structural development of the human brain.","authors":"Yue Li, Qinyao Sun, Shunli Zhu, Congying Chu, Jiaojian Wang","doi":"10.7554/eLife.96020","DOIUrl":"10.7554/eLife.96020","url":null,"abstract":"<p><p>Disentangling the evolution mysteries of the human brain has always been an imperative endeavor in neuroscience. Although many previous comparative studies revealed genetic, brain structural and connectivity distinctness between human and other nonhuman primates, the brain evolutional mechanism is still largely unclear. Here, we proposed to embed the brain anatomy of human and macaque in the developmental chronological axis to construct cross-species predictive model to quantitatively characterize brain evolution using two large public human and macaque datasets. We observed that applying the trained models within-species could well predict the chronological age. Interestingly, we found the model trained in macaque showed a higher accuracy in predicting the chronological age of human than the model trained in human in predicting the chronological age of macaque. The cross-application of the trained model introduced an individual brain cross-species age gap index to quantify the cross-species discrepancy along the temporal axis of brain development and was found to be associated with the behavioral performance in visual acuity test and picture vocabulary test in human. Taken together, our study situated the cross-species brain development along the chronological axis, which highlighted the disproportionately anatomical development in human brain to extend our understanding of the potential evolutionary effects.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799589","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
Polarised moonlight guides nocturnal bull ants home. 偏振月光指引夜行牛蚁回家。
IF 6.4 1区 生物学
eLife Pub Date : 2024-12-09 DOI: 10.7554/eLife.97615
Cody A Freas, Ajay Narenda, Trevor Murray, Ken Cheng
{"title":"Polarised moonlight guides nocturnal bull ants home.","authors":"Cody A Freas, Ajay Narenda, Trevor Murray, Ken Cheng","doi":"10.7554/eLife.97615","DOIUrl":"10.7554/eLife.97615","url":null,"abstract":"<p><p>For the first time in any animal, we show that nocturnal bull ants use the exceedingly dim polarisation pattern produced by the moon for overnight navigation. The sun or moon can provide directional information via their position; however, they can often be obstructed by clouds, canopy, or the horizon. Despite being hidden, these bodies can still provide compass information through the polarised light pattern they produce/reflect. Sunlight produces polarised light patterns across the overhead sky as it enters the atmosphere, and solar polarised light is a well-known compass cue for navigating animals. Moonlight produces an analogous pattern, albeit a million times dimmer than sunlight. Here, we show evidence that polarised moonlight forms part of the celestial compass of navigating nocturnal ants. Nocturnal bull ants leave their nest at twilight and rely heavily on the overhead solar polarisation pattern to navigate. Yet many foragers return home overnight when the sun cannot guide them. We demonstrate that these bull ants use polarised moonlight to navigate home during the night, by rotating the overhead polarisation pattern above homing ants, who alter their headings in response. Furthermore, these ants can detect this cue throughout the lunar month, even under crescent moons, when polarised light levels are at their lowest. Finally, we show the long-term incorporation of this moonlight pattern into the ants' path integration system throughout the night for homing, as polarised sunlight is incorporated throughout the day.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799920","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
Endogenous oligomer formation underlies DVL2 condensates and promotes Wnt/β-catenin signaling.
IF 6.4 1区 生物学
eLife Pub Date : 2024-12-09 DOI: 10.7554/eLife.96841
Senem Ntourmas, Martin Sachs, Petra Paclíková, Martina Brückner, Vítězslav Bryja, Jürgen Behrens, Dominic B Bernkopf
{"title":"Endogenous oligomer formation underlies DVL2 condensates and promotes Wnt/β-catenin signaling.","authors":"Senem Ntourmas, Martin Sachs, Petra Paclíková, Martina Brückner, Vítězslav Bryja, Jürgen Behrens, Dominic B Bernkopf","doi":"10.7554/eLife.96841","DOIUrl":"10.7554/eLife.96841","url":null,"abstract":"<p><p>Activation of the Wnt/β-catenin pathway crucially depends on the polymerization of dishevelled 2 (DVL2) into biomolecular condensates. However, given the low affinity of known DVL2 self-interaction sites and its low cellular concentration, it is unclear how polymers can form. Here, we detect oligomeric DVL2 complexes at endogenous protein levels in human cell lines, using a biochemical ultracentrifugation assay. We identify a low-complexity region (LCR4) in the C-terminus whose deletion and fusion decreased and increased the complexes, respectively. Notably, LCR4-induced complexes correlated with the formation of microscopically visible multimeric condensates. Adjacent to LCR4, we mapped a conserved domain (CD2) promoting condensates only. Molecularly, LCR4 and CD2 mediated DVL2 self-interaction via aggregating residues and phenylalanine stickers, respectively. Point mutations inactivating these interaction sites impaired Wnt pathway activation by DVL2. Our study discovers DVL2 complexes with functional importance for Wnt/β-catenin signaling. Moreover, we provide evidence that DVL2 condensates form in two steps by pre-oligomerization via high-affinity interaction sites, such as LCR4, and subsequent condensation via low-affinity interaction sites, such as CD2.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11627551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799602","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
Maternal obesity may disrupt offspring metabolism by inducing oocyte genome hyper-methylation via increased DNMTs.
IF 6.4 1区 生物学
eLife Pub Date : 2024-12-06 DOI: 10.7554/eLife.97507
Shuo Chao, Jun Lu, Li-Jun Li, Hong-Yan Guo, Kuipeng Xu, Ning Wang, Shu-Xian Zhao, Xiao-Wen Jin, Shao-Ge Wang, Shen Yin, Wei Shen, Ming-Hui Zhao, Gui-An Huang, Qing-Yuan Sun, Zhao-Jia Ge
{"title":"Maternal obesity may disrupt offspring metabolism by inducing oocyte genome hyper-methylation via increased DNMTs.","authors":"Shuo Chao, Jun Lu, Li-Jun Li, Hong-Yan Guo, Kuipeng Xu, Ning Wang, Shu-Xian Zhao, Xiao-Wen Jin, Shao-Ge Wang, Shen Yin, Wei Shen, Ming-Hui Zhao, Gui-An Huang, Qing-Yuan Sun, Zhao-Jia Ge","doi":"10.7554/eLife.97507","DOIUrl":"10.7554/eLife.97507","url":null,"abstract":"<p><p>Maternal obesity has deleterious effects on the process of establishing oocyte DNA methylation; yet the underlying mechanisms remain unclear. Here, we found that maternal obesity disrupted the genomic methylation of oocytes using a high-fat diet (HFD) induced mouse model, at least a part of which was transmitted to the F2 oocytes and livers via females. We further examined the metabolome of serum and found that the serum concentration of melatonin was reduced. Exogenous melatonin treatment significantly reduced the hyper-methylation of HFD oocytes, and the increased expression of DNMT3a and DNMT1 in HFD oocytes was also decreased. These suggest that melatonin may play a key role in the disrupted genomic methylation in the oocytes of obese mice. To address how melatonin regulates the expression of DNMTs, the function of melatonin was inhibited or activated upon oocytes. Results revealed that melatonin may regulate the expression of DNMTs via the cAMP/PKA/CREB pathway. These results suggest that maternal obesity induces genomic methylation alterations in oocytes, which can be partly transmitted to F2 in females, and that melatonin is involved in regulating the hyper-methylation of HFD oocytes by increasing the expression of DNMTs via the cAMP/PKA/CREB pathway.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142789419","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
Increased inflammatory signature in myeloid cells of non-small cell lung cancer patients with high clonal hematopoiesis burden.
IF 6.4 1区 生物学
eLife Pub Date : 2024-12-06 DOI: 10.7554/eLife.96951
Hyungtai Sim, Hyun Jung Park, Geun-Ho Park, Yeon Jeong Kim, Woong-Yang Park, Se-Hoon Lee, Murim Choi
{"title":"Increased inflammatory signature in myeloid cells of non-small cell lung cancer patients with high clonal hematopoiesis burden.","authors":"Hyungtai Sim, Hyun Jung Park, Geun-Ho Park, Yeon Jeong Kim, Woong-Yang Park, Se-Hoon Lee, Murim Choi","doi":"10.7554/eLife.96951","DOIUrl":"10.7554/eLife.96951","url":null,"abstract":"<p><p>Clonal hematopoiesis of indeterminate potential (CHIP) allows estimation of clonal dynamics and documentation of somatic mutations in the hematopoietic system. Recent studies utilizing large cohorts of the general population and patients have revealed significant associations of CHIP burden with age and disease status, including in cancer and chronic diseases. An increasing number of cancer patients are treated with immune checkpoint inhibitors (ICIs), but the association of ICI response in non-small cell lung cancer (NSCLC) patients with CHIP burden remains to be determined. We collected blood samples from 100 metastatic NSCLC patients before and after ICI for high-depth sequencing of the CHIP panel and 63 samples for blood single-cell RNA sequencing. Whole exome sequencing was performed in an independent replication cohort of 180 patients. The impact of CHIP status on the immunotherapy response was not significant. However, metastatic lung cancer patients showed higher CHIP prevalence (44/100 for patients vs. 5/42 for controls; p = 0.01). In addition, lung squamous cell carcinoma (LUSC) patients showed increased burden of larger clones compared to lung adenocarcinoma (LUAD) patients (8/43 for LUSC vs. 2/50 for LUAD; p = 0.04). Furthermore, single-cell RNA-seq analysis of the matched patients showed significant enrichment of inflammatory pathways mediated by NF-κB in myeloid clusters of the severe CHIP group. Our findings suggest minimal involvement of CHIP mutation and clonal dynamics during immunotherapy but a possible role of CHIP as an indicator of immunologic response in NSCLC patients.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784651","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
Single-nucleus transcriptomics reveal the differentiation trajectories of periosteal skeletal/stem progenitor cells in bone regeneration.
IF 6.4 1区 生物学
eLife Pub Date : 2024-12-06 DOI: 10.7554/eLife.92519
Simon Perrin, Maria Ethel, Vincent Bretegnier, Cassandre Goachet, Cécile-Aurore Wotawa, Marine Luka, Fanny Coulpier, Cécile Masson, Mickael Ménager, Céline Colnot
{"title":"Single-nucleus transcriptomics reveal the differentiation trajectories of periosteal skeletal/stem progenitor cells in bone regeneration.","authors":"Simon Perrin, Maria Ethel, Vincent Bretegnier, Cassandre Goachet, Cécile-Aurore Wotawa, Marine Luka, Fanny Coulpier, Cécile Masson, Mickael Ménager, Céline Colnot","doi":"10.7554/eLife.92519","DOIUrl":"10.7554/eLife.92519","url":null,"abstract":"<p><p>Bone regeneration is mediated by skeletal stem/progenitor cells (SSPCs) that are mainly recruited from the periosteum after bone injury. The composition of the periosteum and the steps of SSPC activation and differentiation remain poorly understood. Here, we generated a single-nucleus atlas of the periosteum at steady state and of the fracture site during the early stages of bone repair (https://fracture-repair-atlas.cells.ucsc.edu). We identified periosteal SSPCs expressing stemness markers (<i>Pi16</i> and <i>Ly6a</i>/SCA1) and responding to fracture by adopting an injury-induced fibrogenic cell (IIFC) fate, prior to undergoing osteogenesis or chondrogenesis. We identified distinct gene cores associated with IIFCs and their engagement into osteogenesis and chondrogenesis involving Notch, Wnt, and the circadian clock signaling, respectively. Finally, we show that IIFCs are the main source of paracrine signals in the fracture environment, suggesting a crucial paracrine role of this transient IIFC population during fracture healing. Overall, our study provides a complete temporal topography of the early stages of fracture healing and the dynamic response of periosteal SSPCs to injury, redefining our knowledge of bone regeneration.</p>","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142789423","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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