Developmental cellPub Date : 2025-10-20DOI: 10.1016/j.devcel.2025.09.017
Gopal Chovatiya, Sean Y Huang, Alex B Wang, Philip Versluis, Chris K Bai, Michael DeBerardine, Yu-Ching Liao, Judhajeet Ray, Abdullah Ozer, John T Lis, Tudorita Tumbar
{"title":"Cell-type-specific RNA polymerase II activity maps in intact tissues provide a gateway to mammalian gene regulatory mechanisms in vivo.","authors":"Gopal Chovatiya, Sean Y Huang, Alex B Wang, Philip Versluis, Chris K Bai, Michael DeBerardine, Yu-Ching Liao, Judhajeet Ray, Abdullah Ozer, John T Lis, Tudorita Tumbar","doi":"10.1016/j.devcel.2025.09.017","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.09.017","url":null,"abstract":"<p><p>Accessing ongoing RNA polymerase II (RNA Pol II) activity in specific cell types within intact tissue is critical to reveal regulatory mechanisms of development. We developed precision run-on in cell-type-specific in vivo system followed by sequencing (PReCIS-seq), a method combining Cre-inducible GFP tagging of endogenous RNA Pol II with transcriptional run-on and GFP immunoprecipitation, to map transcriptionally engaged RNA Pol II genome-wide in targeted cell types of mouse tissues. Applied to keratinocytes within intact skin, PReCIS-seq demonstrates that transcriptionally activated functions of biological transitions generally employ both RNA Pol II promoter-recruitment and promoter-proximal pause-release mechanisms. A global RNA Pol II regulatory polarization features extreme pausing levels at cellular safeguarding vs. lineage identity genes across development and homeostasis. This polarization is associated with distinct proximal-promoter structures, distinguishing high-paused genes with restricted RNA Pol II pause-release from low-paused genes undergoing rapid RNA Pol II firing into productive elongation. PReCIS-seq also identifies active enhancers based on divergent transcription. This approach enables high-resolution, cell-type-specific analysis of RNA Pol II dynamics in intact tissues across mammalian development, homeostasis, and disease.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Developmental cellPub Date : 2025-10-20DOI: 10.1016/j.devcel.2025.09.008
Yan G Zhao, Hong Zhang
{"title":"TfR in focus: Orchestrating autophagosome biogenesis.","authors":"Yan G Zhao, Hong Zhang","doi":"10.1016/j.devcel.2025.09.008","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.09.008","url":null,"abstract":"<p><p>Transferrin receptors, responsible for iron importation into cells, exhibit additional iron-independent functions. In this issue, Puri et al. reveal that the transferrin receptor recruits the VPS34 complex I, stimulating PI(3)P synthesis. This PI(3)P production aids in autophagosome elongation and closure by facilitating recruitment of the LC3 conjugation system and ESCRT, respectively.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"60 20","pages":"2697-2699"},"PeriodicalIF":8.7,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Developmental cellPub Date : 2025-10-20DOI: 10.1016/j.devcel.2025.09.018
Xin-Xin Yu, Xin Wang, Liu Yang, Mao-Yang He, Xi Wang, Yi-Ning Wang, Ke-Ran Li, Cheng-Ran Xu
{"title":"Reconstructing human pancreatic gene networks enhances stem cell-derived β cell induction.","authors":"Xin-Xin Yu, Xin Wang, Liu Yang, Mao-Yang He, Xi Wang, Yi-Ning Wang, Ke-Ran Li, Cheng-Ran Xu","doi":"10.1016/j.devcel.2025.09.018","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.09.018","url":null,"abstract":"<p><p>Generating functional β cells from stem cells remains a major challenge in regenerative medicine due to the incomplete recapitulation of human pancreatic development in vitro. By integrating newly generated human single-cell RNA sequencing (RNA-seq) datasets (Carnegie stages 10-15) with existing data, we mapped gene co-expression networks (GCNs) underlying pancreatic lineage progression in humans and mice. We observed significant species-specific differences in GCN robustness and dorsal-ventral propensity for progenitor development. Benchmarking three common differentiation protocols against the in vivo datasets showed that they fail to reproduce human-like GCNs, thereby limiting stem cell-derived insulin-secreting β cell (SC-β cell) induction efficiency. To address this, we developed a protocol that reconstructs human pancreatic GCN dynamics, shortens the induction period to 19 days, and achieves up to ∼70% β cell content. SC-islets generated with this method significantly alleviated diabetic symptoms and maintained mature β cell function after transplantation in mice. These findings bridge in vivo mechanisms and in vitro differentiation, advancing stem cell-based therapies.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Developmental cellPub Date : 2025-10-20DOI: 10.1016/j.devcel.2025.09.016
Nian Wang, Jiao Liu, Runliu Wu, Feng Chen, Chunhua Yu, Herbert Zeh, Xianzhong Xiao, Haichao Wang, Timothy R Billiar, Ling Zeng, Jianxin Jiang, Daolin Tang, Rui Kang
{"title":"A non-canonical immunometabolic function of BRD3 during sepsis.","authors":"Nian Wang, Jiao Liu, Runliu Wu, Feng Chen, Chunhua Yu, Herbert Zeh, Xianzhong Xiao, Haichao Wang, Timothy R Billiar, Ling Zeng, Jianxin Jiang, Daolin Tang, Rui Kang","doi":"10.1016/j.devcel.2025.09.016","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.09.016","url":null,"abstract":"<p><p>Sepsis is a life-threatening condition characterized by a dysregulated host innate immune response to pathogen infection. Here, we identify a pathological role for bromodomain-containing 3 (BRD3) in driving septic shock by upregulating aconitate decarboxylase 1 (ACOD1) in monocytes and macrophages via a non-canonical pathway. Mechanistically, lipopolysaccharide triggers an interaction between BRD3 and tripartite motif containing 21 (TRIM21), which activates CREB binding lysine acetyltransferase (CREBBP) via its E3 ligase activity, facilitating CREBBP's binding to and acetylation of cyclic adenosine monophophate (cAMP)-response-element-binding protein 1 (CREB1). BRD3 then recognizes and phosphorylates acetylated CREB1 at the transcription-activating site, thereby upregulating ACOD1 transcription. In four murine models of infection, myeloid-specific Brd3 deletion (Brd3<sup>Mye</sup><sup>-/-</sup>) or pharmacological intervention using small-molecule inhibitor OTX015 confers significant protection, reducing systemic inflammation and organ injury, similar to the effects observed in Acod1<sup>Mye-/-</sup> mice. In patients with sepsis, elevated BRD3 levels correlate with accelerated inflammation, increased disease severity, and a greater risk of in-hospital death. These findings establish BRD3 as a potential therapeutic target for managing infection-associated immune dysregulation.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":" ","pages":""},"PeriodicalIF":8.7,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Developmental cellPub Date : 2025-10-20DOI: 10.1016/j.devcel.2025.09.010
Hemmo Meyer, Bojana Kravic
{"title":"ATG9 assists lipid replenishment for lysosome membrane repair.","authors":"Hemmo Meyer, Bojana Kravic","doi":"10.1016/j.devcel.2025.09.010","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.09.010","url":null,"abstract":"<p><p>Lysosomal membranes can be permeabilized under various conditions with detrimental consequences for the cell. In this issue, de Tito et al. report that the lipid scramblase ATG9, best known for its role in autophagosome formation, helps distribute lipids from the ER to reseal the limiting membrane and restore lysosomal function.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"60 20","pages":"2701-2702"},"PeriodicalIF":8.7,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Developmental cellPub Date : 2025-10-20DOI: 10.1016/j.devcel.2025.09.014
Keqiang Wu
{"title":"When flowers fall: Calcium-driven epigenetic silencing links drought to reproductive loss in tomato.","authors":"Keqiang Wu","doi":"10.1016/j.devcel.2025.09.014","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.09.014","url":null,"abstract":"<p><p>In this issue of Developmental Cell, Ge et al. <sup>1</sup> reveal that drought-induced calcium signaling in tomato activates the SlCBL11-SlCIPK10 complex, which phosphorylates the chromatin protein SlLHP1b. This modification enhances H3K27me3-mediated repression of stamen SlYUC genes, lowering auxin levels and collapsing the abscission zone gradient to trigger flower drop.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"60 20","pages":"2699-2700"},"PeriodicalIF":8.7,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Developmental cellPub Date : 2025-10-15DOI: 10.1016/j.devcel.2025.09.021
Meng-Jia Wang, Yi-Fang Tsay
{"title":"NRT1.1 is a versatile coordinator of nutrient and hormone signaling in plants","authors":"Meng-Jia Wang, Yi-Fang Tsay","doi":"10.1016/j.devcel.2025.09.021","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.09.021","url":null,"abstract":"The nitrate transceptor NRT1.1 detects external nitrate levels to regulate nitrate-induced transcriptional responses, auxin transport, and phosphate starvation responses in plants. A study by Ma et al.<span><span><sup>1</sup></span></span> redefines our understanding of abscisic acid (ABA) perception and reveals NRT1.1 as a signaling hub that integrates the nutrient status with abiotic stresses.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"1 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145289268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Degradation of detrimental microRNAs safeguards the fertilized egg cells to establish an ECS-dependent polytubey block in Arabidopsis","authors":"Kun Shen, Mengxue Qu, Xuemei Zhou, Yingying Guo, Yicheng Zhong, Meng-xiang Sun, Peng Zhao","doi":"10.1016/j.devcel.2025.09.013","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.09.013","url":null,"abstract":"Fertilization of the egg cell by more than one sperm cell results in aneuploidy and genomic dysfunction. To avoid this, flowering plants have intricate polytubey block mechanisms that prevent additional pollen tubes from entering the ovule. In one mechanism for blocking polytubey, the fertilized egg cell secretes the aspartic endopeptidases EGG CELL-SPECIFIC1 (ECS1) and ECS2, which degrade pollen tube attractants. However, the mechanism underlying the egg-cell-specific expression of <em>ECS1</em> and <em>ECS2</em> was unknown. Here, we demonstrate that in <em>Arabidopsis thaliana</em> egg cells, SMALL RNA DEGRADING NUCLEASE (SDN) degrades microRNAs (miRNAs) targeting <em>ECS</em> genes, thereby allowing ECS1 and ECS2 to accumulate in egg cells to establish the polytubey block. Like <em>Arabidopsis ecs1 ecs2</em> mutants, <em>sdn1 sdn2 sdn3</em> mutants exhibited polytubey, as did plants specifically overexpressing miRNAs targeting <em>ECS</em> genes in egg cells. Therefore, the SDN-miRNA-ECS module allows ECS accumulation in egg cells to block polytubey.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"120 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Developmental cellPub Date : 2025-10-09DOI: 10.1016/j.devcel.2025.09.011
Aurélie Lardenois, Antonio Suglia, Chad Lewis Moore, Bertrand Evrard, Laurence Noël, Paul Rivaud, Aurore Besson, Maryne Toupin, Joséphine Blévinal, Corentin Dumortier, Simon Léonard, Laurianne Lesné, Isabelle Coiffec, Serge Nef, Vincent Lavoué, Anthony Bretaudeau, Alain Chédotal, Séverine Mazaud-Guittot, Frédéric Chalmel, Antoine Dominique Rolland
{"title":"Single-cell exploration of gonadal somatic cell lineage specification during human sex determination","authors":"Aurélie Lardenois, Antonio Suglia, Chad Lewis Moore, Bertrand Evrard, Laurence Noël, Paul Rivaud, Aurore Besson, Maryne Toupin, Joséphine Blévinal, Corentin Dumortier, Simon Léonard, Laurianne Lesné, Isabelle Coiffec, Serge Nef, Vincent Lavoué, Anthony Bretaudeau, Alain Chédotal, Séverine Mazaud-Guittot, Frédéric Chalmel, Antoine Dominique Rolland","doi":"10.1016/j.devcel.2025.09.011","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.09.011","url":null,"abstract":"Gonad development is an exciting model to study cell fate commitment. A better understanding of sex determination requires the identification of all involved cell types and their dynamic expression programs. Here, we present an atlas of 128,000 single cells from human gonads between 5 and 12 post-conceptional weeks. A focused analysis of somatic cells uncovered a population of bipotential progenitors derived from the coelomic epithelium of both testes and ovaries, which may have the capacity to commit to either a steroidogenic or a supporting fate. Moreover, our analyses suggest that early supporting cells, prior to differentiation into Sertoli or pre-granulosa cells, also give rise to the <em>rete testis</em>/<em>ovarii</em> and that the ovary retains the capacity to feed the supporting cell pool for an extended period of time, directly from the surface epithelium. Finally, the potential involvement of the gonadotropin releasing hormone (GnRH) signaling pathway in regulating testis differentiation was assessed <em>ex vivo</em>.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"50 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Developmental cellPub Date : 2025-10-09DOI: 10.1016/j.devcel.2025.09.012
Zuoxing Wu, Na Li, Zhengqiong Luo, Zihan Chen, Xuemei He, Fan Shi, Jie Han, Haitao Huang, Baohong Shi, Long Zhang, Yu Li, Junmin Shen, Seoyeon Bok, Jun Sun, Xing Niu, Ke Mo, Pengbin Yin, Lige Leng, Xin Wang, Jie Zhang, Ren Xu
{"title":"The p75 neurotrophin receptor controls the skeletal stem cell niche through sensory innervation","authors":"Zuoxing Wu, Na Li, Zhengqiong Luo, Zihan Chen, Xuemei He, Fan Shi, Jie Han, Haitao Huang, Baohong Shi, Long Zhang, Yu Li, Junmin Shen, Seoyeon Bok, Jun Sun, Xing Niu, Ke Mo, Pengbin Yin, Lige Leng, Xin Wang, Jie Zhang, Ren Xu","doi":"10.1016/j.devcel.2025.09.012","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.09.012","url":null,"abstract":"Low bone mass is frequently observed in Alzheimer’s disease (AD), yet the underlying mechanisms remain poorly understood. In this study, we demonstrate that sensory nerves constitute a critical component of the skeletal stem cell (SSC) niche. Deletion of the neurotrophin receptor p75NTR in neurons or sensory-specific cells, but not in osteogenic or sympathetic cells, resulted in reduced sensory innervation, disrupted SSC homeostasis, and significant bone loss. Although a cell-intrinsic role of p75NTR in SSCs cannot be ruled out, further experiments involving sensory denervation or transplantation into hosts with sensory-neuron-specific p75NTR deficiency confirmed impaired SSC osteogenesis. Mechanistically, p75NTR controls the expression of neuronal osteopontin (SPP1), which in turn promotes SSC self-renewal and osteogenic differentiation. Notably, this p75NTR-SPP1 signaling axis was found to be disrupted in AD mouse models, offering a direct mechanistic explanation for AD-associated osteopenia and highlighting the therapeutic potential of targeting neural control of SSCs.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"9 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}