Developmental cell最新文献

Cell-type-specific RNA polymerase II activity maps in intact tissues provide a gateway to mammalian gene regulatory mechanisms in vivo. 完整组织中细胞类型特异性RNA聚合酶II活性图谱为研究哺乳动物体内基因调控机制提供了一个途径。

IF 8.7 1区生物学

Developmental cell Pub Date : 2025-10-20 DOI: 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":"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.","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}

引用次数: 0

TfR in focus: Orchestrating autophagosome biogenesis. 聚焦TfR：协调自噬体的生物发生。

IF 8.7 1区生物学

Developmental cell Pub Date : 2025-10-20 DOI: 10.1016/j.devcel.2025.09.008

Yan G Zhao, Hong Zhang

引用次数: 0

Reconstructing human pancreatic gene networks enhances stem cell-derived β cell induction. 重建人类胰腺基因网络增强干细胞来源的β细胞诱导。

IF 8.7 1区生物学

Developmental cell Pub Date : 2025-10-20 DOI: 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":"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.","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}

引用次数: 0

A non-canonical immunometabolic function of BRD3 during sepsis. 败血症期间BRD3的非典型免疫代谢功能。

IF 8.7 1区生物学

Developmental cell Pub Date : 2025-10-20 DOI: 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":"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 (Brd3Mye-/-) or pharmacological intervention using small-molecule inhibitor OTX015 confers significant protection, reducing systemic inflammation and organ injury, similar to the effects observed in Acod1Mye-/- 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.","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}

引用次数: 0

ATG9 assists lipid replenishment for lysosome membrane repair. ATG9协助脂质补充，促进溶酶体膜修复。

IF 8.7 1区生物学

Developmental cell Pub Date : 2025-10-20 DOI: 10.1016/j.devcel.2025.09.010

Hemmo Meyer, Bojana Kravic

引用次数: 0

When flowers fall: Calcium-driven epigenetic silencing links drought to reproductive loss in tomato. 当花朵凋谢：钙驱动的表观遗传沉默将干旱与番茄的繁殖丧失联系起来。

IF 8.7 1区生物学

Developmental cell Pub Date : 2025-10-20 DOI: 10.1016/j.devcel.2025.09.014

Keqiang Wu

引用次数: 0

NRT1.1 is a versatile coordinator of nutrient and hormone signaling in plants NRT1.1是植物营养和激素信号的多功能协调者

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-10-15 DOI: 10.1016/j.devcel.2025.09.021

Meng-Jia Wang, Yi-Fang Tsay

引用次数: 0

Degradation of detrimental microRNAs safeguards the fertilized egg cells to establish an ECS-dependent polytubey block in Arabidopsis 有害microrna的降解保护受精卵细胞在拟南芥中建立ecs依赖性多管阻滞

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-10-13 DOI: 10.1016/j.devcel.2025.09.013

Kun Shen, Mengxue Qu, Xuemei Zhou, Yingying Guo, Yicheng Zhong, Meng-xiang Sun, Peng Zhao

{"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 ECS1 and ECS2 was unknown. Here, we demonstrate that in Arabidopsis thaliana egg cells, SMALL RNA DEGRADING NUCLEASE (SDN) degrades microRNAs (miRNAs) targeting ECS genes, thereby allowing ECS1 and ECS2 to accumulate in egg cells to establish the polytubey block. Like Arabidopsis ecs1 ecs2 mutants, sdn1 sdn2 sdn3 mutants exhibited polytubey, as did plants specifically overexpressing miRNAs targeting ECS 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}

引用次数: 0

Single-cell exploration of gonadal somatic cell lineage specification during human sex determination 人类性别决定过程中性腺体细胞谱系的单细胞探索

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-10-09 DOI: 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 rete testis/ovarii 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 ex vivo.","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}

引用次数: 0

The p75 neurotrophin receptor controls the skeletal stem cell niche through sensory innervation p75神经营养因子受体通过感觉神经支配控制骨骼干细胞生态位

IF 11.8 1区生物学

Developmental cell Pub Date : 2025-10-09 DOI: 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}

引用次数: 0