Developmental cell最新文献

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A subset of neutrophils activates anti-tumor immunity and inhibits non-small-cell lung cancer progression 中性粒细胞亚群可激活抗肿瘤免疫力并抑制非小细胞肺癌的进展
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-11-07 DOI: 10.1016/j.devcel.2024.10.010
Zhen Tang, Jing Hu, Xu-Chang Li, Wei Wang, Han-Yue Zhang, Yu-Yao Guo, Xin Shuai, Qian Chu, Conghua Xie, Dandan Lin, Bo Zhong
{"title":"A subset of neutrophils activates anti-tumor immunity and inhibits non-small-cell lung cancer progression","authors":"Zhen Tang, Jing Hu, Xu-Chang Li, Wei Wang, Han-Yue Zhang, Yu-Yao Guo, Xin Shuai, Qian Chu, Conghua Xie, Dandan Lin, Bo Zhong","doi":"10.1016/j.devcel.2024.10.010","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.010","url":null,"abstract":"Neutrophils in the tumor microenvironment (TME) are heterogeneous populations associated with cancer prognosis and immunotherapy. However, the plasticity and function of heterogeneous neutrophils in the TME of non-small-cell lung cancer (NSCLC) remain unclear. Here, we show that neutrophils produce high levels of interleukin (IL)-8, which induce the differentiation of CD74<sup>high</sup>SiglecF<sup>low</sup> neutrophils and suppress the generation of CD74<sup>low</sup>SiglecF<sup>high</sup> neutrophils in the TME of IL-8-humanized NSCLC mice. The CD74<sup>high</sup>SiglecF<sup>low</sup> neutrophils boost anti-tumor T cell responses via antigen cross-presentation. Deleting CD74 in IL-8-humanized neutrophils impairs T cell activation and exacerbates NSCLC progression, whereas a CD74 agonist enhances T cell activation and the efficacy of anti-programmed cell death 1 (PD-1) or osimertinib therapies. Additionally, the CD74<sup>high</sup>CD63<sup>low</sup> neutrophils in the TME and peripheral blood of advanced NSCLC patients phenocopy the CD74<sup>high</sup>SiglecF<sup>low</sup> neutrophils in the TME of NSCLC mice and correlate well with the responsiveness to anti-PD-1 plus chemotherapies. These findings demonstrate an IL-8-CD74<sup>high</sup> neutrophil axis that promotes anti-tumor immunity in NSCLC.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"95 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594592","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
Autophagy-dependent splicing control directs translation toward inflammation during senescence 依赖自噬的剪接控制引导衰老过程中的炎症翻译
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-11-06 DOI: 10.1016/j.devcel.2024.10.008
Jaejin Kim, Yeonghyeon Lee, Taerang Jeon, Seonmin Ju, Jong-Seo Kim, Mi-Sung Kim, Chanhee Kang
{"title":"Autophagy-dependent splicing control directs translation toward inflammation during senescence","authors":"Jaejin Kim, Yeonghyeon Lee, Taerang Jeon, Seonmin Ju, Jong-Seo Kim, Mi-Sung Kim, Chanhee Kang","doi":"10.1016/j.devcel.2024.10.008","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.008","url":null,"abstract":"The cellular proteome determines the functional state of cells and is often skewed to direct pathological conditions. Autophagy shapes cellular proteomes primarily through lysosomal degradation of either damaged or unnecessary proteins. Here, we show that autophagy directs the senescence-specific translatome to fuel inflammation by coupling selective protein degradation with alternative splicing. RNA splicing is significantly altered during senescence, some of which surprisingly depend on autophagy, including exon 5 skipping of the translation regulator <em>EIF4H</em>. Systematic translatome profiling indicates that this event is key to the translational bias toward inflammation in senescence. Autophagy promotes these changes by selectively degrading the splicing regulator splicing factor proline and glutamine rich (SFPQ) via the autophagy receptor NBR1. These autophagy-centric inflammatory controls appear to be conserved during human tissue aging and cancer. Our work highlights the role of autophagy in the on-demand functional remodeling of cellular proteomes as well as the crosstalk between autophagy, alternative splicing, and inflammatory translation.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"22 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589075","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
Comparative analysis of tongue cancer organoids among patients identifies the heritable nature of minimal residual disease 对不同患者的舌癌组织细胞进行比较分析,确定极小残留病的遗传性质
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-11-05 DOI: 10.1016/j.devcel.2024.10.007
Miwako Sase, Taku Sato, Hajime Sato, Fuyuki Miya, Shicheng Zhang, Hiroshi Haeno, Mihoko Kajita, Tadahide Noguchi, Yoshiyuki Mori, Toshiaki Ohteki
{"title":"Comparative analysis of tongue cancer organoids among patients identifies the heritable nature of minimal residual disease","authors":"Miwako Sase, Taku Sato, Hajime Sato, Fuyuki Miya, Shicheng Zhang, Hiroshi Haeno, Mihoko Kajita, Tadahide Noguchi, Yoshiyuki Mori, Toshiaki Ohteki","doi":"10.1016/j.devcel.2024.10.007","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.007","url":null,"abstract":"The relapse of tongue cancer (TC) after chemotherapy is caused by minimal residual disease (MRD), which is a few remaining cancer cells after chemotherapy. To understand the mechanism of MRD in TC, we created a library of TC organoids (TCOs) from 28 untreated TC patients at diverse ages and cancer stages. These TCOs reproduced the primary TC tissues both <em>in vitro</em> and in a xenograft model, and several TCO lines survived after cisplatin treatment (chemo-resistant TCOs). Of note, the chemo-resistant TCOs showed “heritable” embryonic diapause-like features before treatment and activation of the autophagy and cholesterol biosynthetic pathways. Importantly, inhibiting these pathways with specific inhibitors converted the chemo-resistant TCOs into chemo-sensitive TCOs. Conversely, autophagy activation with mTOR inhibitors conferred chemo-resistance on the chemo-sensitive TCOs. This unique model provides insights into the mechanism of MRD formation in TCs, leading to effective therapeutic approaches to reduce the recurrence of TC.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"7 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580403","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
Stem cells feel the pain 干细胞感受痛苦
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-11-04 DOI: 10.1016/j.devcel.2024.09.028
Jingyu Peng, Mark J. Khoury, Ya-Chieh Hsu
{"title":"Stem cells feel the pain","authors":"Jingyu Peng, Mark J. Khoury, Ya-Chieh Hsu","doi":"10.1016/j.devcel.2024.09.028","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.09.028","url":null,"abstract":"Pain is a sensation that signals the presence of inflammation or injury. In this issue of <em>Developmental Cell</em>, Ben-Shaanan et al.<span><span><sup>1</sup></span></span> show that beyond its sensory function, pain can activate hair follicle stem cells (HFSCs) by controlling their niche.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"26 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580052","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 mobile miR160-triggered transcriptional axis controls root stem cell niche maintenance and regeneration in Arabidopsis miR160触发的移动转录轴控制拟南芥根干细胞龛的维持和再生
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-11-01 DOI: 10.1016/j.devcel.2024.10.006
Xixi Cai, Hang Zhang, Changqing Mu, Yanjun Chen, Chongzhen He, Mingyu Liu, Thomas Laux, Limin Pi
{"title":"A mobile miR160-triggered transcriptional axis controls root stem cell niche maintenance and regeneration in Arabidopsis","authors":"Xixi Cai, Hang Zhang, Changqing Mu, Yanjun Chen, Chongzhen He, Mingyu Liu, Thomas Laux, Limin Pi","doi":"10.1016/j.devcel.2024.10.006","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.006","url":null,"abstract":"In multicellular organisms, communication between cells is vital for their fate determination. In plants, the quiescent center (QC) signals to adjacent stem cells to maintain them undifferentiated. However, how surrounding stem cells instruct the QC remains poorly understood. Here, we show that in the <em>Arabidopsis</em> root, microRNA160 (miR160) moves from stele stem cells (SSCs) to the QC, where it degrades the mRNAs of two auxin response factors, <em>ARF10</em> and <em>ARF17</em>. This degradation relieves <em>BRAVO</em> from direct transcriptional repression, maintaining QC quiescence. We further identify that blocking miR160 movement due to DNA damage-induced SSC death and restricted symplastic transport reduces <em>BRAVO</em> and <em>WOX5</em> expression, leading to QC division to replenish damaged stem cells during root regeneration. Together, our results demonstrate that a transcriptional axis initiated by mobile miR160 regulates the QC and stem cell behavior, advancing our understanding of the communication between stem cells and their surrounding cellular environment.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"87 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562138","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
Combinatorial transcription factor binding encodes cis-regulatory wiring of mouse forebrain GABAergic neurogenesis 组合转录因子结合编码小鼠前脑GABA能神经发生的顺式调控线路
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-10-30 DOI: 10.1016/j.devcel.2024.10.004
Rinaldo Catta-Preta, Susan Lindtner, Athena Ypsilanti, Nicolas Seban, James D. Price, Armen Abnousi, Linda Su-Feher, Yurong Wang, Karol Cichewicz, Sally A. Boerma, Ivan Juric, Ian R. Jones, Jennifer A. Akiyama, Ming Hu, Yin Shen, Axel Visel, Len A. Pennacchio, Diane E. Dickel, John L.R. Rubenstein, Alex S. Nord
{"title":"Combinatorial transcription factor binding encodes cis-regulatory wiring of mouse forebrain GABAergic neurogenesis","authors":"Rinaldo Catta-Preta, Susan Lindtner, Athena Ypsilanti, Nicolas Seban, James D. Price, Armen Abnousi, Linda Su-Feher, Yurong Wang, Karol Cichewicz, Sally A. Boerma, Ivan Juric, Ian R. Jones, Jennifer A. Akiyama, Ming Hu, Yin Shen, Axel Visel, Len A. Pennacchio, Diane E. Dickel, John L.R. Rubenstein, Alex S. Nord","doi":"10.1016/j.devcel.2024.10.004","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.004","url":null,"abstract":"Transcription factors (TFs) bind combinatorially to <em>cis</em>-regulatory elements, orchestrating transcriptional programs. Although studies of chromatin state and chromosomal interactions have demonstrated dynamic neurodevelopmental <em>cis</em>-regulatory landscapes, parallel understanding of TF interactions lags. To elucidate combinatorial TF binding driving mouse basal ganglia development, we integrated chromatin immunoprecipitation sequencing (ChIP-seq) for twelve TFs, H3K4me3-associated enhancer-promoter interactions, chromatin and gene expression data, and functional enhancer assays. We identified sets of putative regulatory elements with shared TF binding (TF-pRE modules) that orchestrate distinct processes of GABAergic neurogenesis and suppress other cell fates. The majority of pREs were bound by one or two TFs; however, a small proportion were extensively bound. These sequences had exceptional evolutionary conservation and motif density, complex chromosomal interactions, and activity as <em>in vivo</em> enhancers. Our results provide insights into the combinatorial TF-pRE interactions that activate and repress expression programs during telencephalon neurogenesis and demonstrate the value of TF binding toward modeling developmental transcriptional wiring.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"26 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542100","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
Comparative single-cell multiome identifies evolutionary changes in neural progenitor cells during primate brain development 单细胞多组比较确定灵长类动物大脑发育过程中神经祖细胞的进化变化
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-10-30 DOI: 10.1016/j.devcel.2024.10.005
Yuting Liu, Xin Luo, Yiming Sun, Kaimin Chen, Ting Hu, Benhui You, Jiahao Xu, Fengyun Zhang, Qing Cheng, Xiaoyu Meng, Tong Yan, Xiang Li, Xiaoxuan Qi, Xiechao He, Xuejiang Guo, Cheng Li, Bing Su
{"title":"Comparative single-cell multiome identifies evolutionary changes in neural progenitor cells during primate brain development","authors":"Yuting Liu, Xin Luo, Yiming Sun, Kaimin Chen, Ting Hu, Benhui You, Jiahao Xu, Fengyun Zhang, Qing Cheng, Xiaoyu Meng, Tong Yan, Xiang Li, Xiaoxuan Qi, Xiechao He, Xuejiang Guo, Cheng Li, Bing Su","doi":"10.1016/j.devcel.2024.10.005","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.005","url":null,"abstract":"Understanding the cellular and genetic mechanisms driving human-specific features of cortical development remains a challenge. We generated a cell-type resolved atlas of transcriptome and chromatin accessibility in the developing macaque and mouse prefrontal cortex (PFC). Comparing with published human data, our findings demonstrate that although the cortex cellular composition is overall conserved across species, progenitor cells show significant evolutionary divergence in cellular properties. Specifically, human neural progenitors exhibit extensive transcriptional rewiring in growth factor and extracellular matrix (ECM) pathways. Expression of the human-specific progenitor marker <em>ITGA2</em> in the fetal mouse cortex increases the progenitor proliferation and the proportion of upper-layer neurons. These transcriptional divergences are primarily driven by altered activity in the distal regulatory elements. The chromatin regions with human-gained accessibility are enriched with human-specific sequence changes and polymorphisms linked to intelligence and neuropsychiatric disorders. Our results identify evolutionary changes in neural progenitors and putative gene regulatory mechanisms shaping primate brain evolution.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"2 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541582","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
An SLC12A9-dependent ion transport mechanism maintains lysosomal osmolarity 依赖 SLC12A9 的离子转运机制维持溶酶体渗透压
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-10-29 DOI: 10.1016/j.devcel.2024.10.003
Roni Levin-Konigsberg, Koushambi Mitra, Kaitlyn Spees, AkshatKumar Nigam, Katherine Liu, Camille Januel, Pravin Hivare, Sophia M. Arana, Laura M. Prolo, Anshul Kundaje, Manuel D. Leonetti, Yamuna Krishnan, Michael C. Bassik
{"title":"An SLC12A9-dependent ion transport mechanism maintains lysosomal osmolarity","authors":"Roni Levin-Konigsberg, Koushambi Mitra, Kaitlyn Spees, AkshatKumar Nigam, Katherine Liu, Camille Januel, Pravin Hivare, Sophia M. Arana, Laura M. Prolo, Anshul Kundaje, Manuel D. Leonetti, Yamuna Krishnan, Michael C. Bassik","doi":"10.1016/j.devcel.2024.10.003","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.003","url":null,"abstract":"Ammonia is a ubiquitous, toxic by-product of cell metabolism. Its high membrane permeability and proton affinity cause ammonia to accumulate inside acidic lysosomes in its poorly membrane-permeant form: ammonium (NH<sub>4</sub><sup>+</sup>). Ammonium buildup compromises lysosomal function, suggesting the existence of mechanisms that protect cells from ammonium toxicity. Here, we identified SLC12A9 as a lysosomal-resident protein that preserves organelle homeostasis by controlling ammonium and chloride levels. SLC12A9 knockout (KO) cells showed grossly enlarged lysosomes and elevated ammonium content. These phenotypes were reversed upon removal of the metabolic source of ammonium or dissipation of the lysosomal pH gradient. Lysosomal chloride increased in SLC12A9 KO cells, and chloride binding by SLC12A9 was required for ammonium transport. Our data indicate that SLC12A9 function is central for the handling of lysosomal ammonium and chloride, an unappreciated, fundamental mechanism of lysosomal physiology that may have special relevance in tissues with elevated ammonia, such as tumors.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"1 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536561","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
EGFR-dependent actomyosin patterning coordinates morphogenetic movements between tissues in Drosophila melanogaster 表皮生长因子受体依赖性肌动蛋白模式协调黑腹果蝇组织间的形态发生运动
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-10-25 DOI: 10.1016/j.devcel.2024.10.002
D. Nathaniel Clarke, Pearson W. Miller, Adam C. Martin
{"title":"EGFR-dependent actomyosin patterning coordinates morphogenetic movements between tissues in Drosophila melanogaster","authors":"D. Nathaniel Clarke, Pearson W. Miller, Adam C. Martin","doi":"10.1016/j.devcel.2024.10.002","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.002","url":null,"abstract":"The movements that give rise to the body’s structure are powered by cell shape changes and rearrangements that are coordinated at supracellular scales. How such cellular coordination arises and integrates different morphogenetic programs is unclear. Using quantitative imaging, we found a complex pattern of adherens junction (AJ) levels in the ectoderm prior to gastrulation onset in <em>Drosophila</em>. AJ intensity exhibited a double-sided gradient, with peaks at the dorsal midline and ventral neuroectoderm. We show that this dorsal-ventral AJ pattern is regulated by epidermal growth factor (EGF) signaling and that this signal is required for ectoderm cell movement during mesoderm invagination and axis extension. We identify AJ levels and junctional actomyosin as downstream effectors of EGFR signaling. Overall, our study demonstrates an EGF-patterned mechanical feedback mechanism that coordinates tissue folding and convergent extension to facilitate embryo-wide gastrulation movements.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"5 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489628","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
PI3K/AKT signaling controls ICM maturation and proper epiblast and primitive endoderm specification in mice PI3K/AKT 信号控制小鼠 ICM 的成熟以及上胚层和原始内胚层的正常分化
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-10-25 DOI: 10.1016/j.devcel.2024.10.001
Anna Geiselmann, Adèle Micouin, Sandrine Vandormael-Pournin, Vincent Laville, Almira Chervova, Sébastien Mella, Pablo Navarro, Michel Cohen-Tannoudji
{"title":"PI3K/AKT signaling controls ICM maturation and proper epiblast and primitive endoderm specification in mice","authors":"Anna Geiselmann, Adèle Micouin, Sandrine Vandormael-Pournin, Vincent Laville, Almira Chervova, Sébastien Mella, Pablo Navarro, Michel Cohen-Tannoudji","doi":"10.1016/j.devcel.2024.10.001","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.10.001","url":null,"abstract":"The inner cell mass (ICM) of early mouse embryos is specified into epiblast (Epi) and primitive endoderm (PrE) lineages during blastocyst formation. The antagonistic transcription factors (TFs) NANOG and GATA-binding protein 6 (GATA6) in combination with fibroblast growth factor (FGF)/extracellular-signal-regulated kinase (ERK) signaling are central actors in ICM fate choice. However, what initiates the specification of ICM progenitors into Epi or PrE and whether other factors are involved in this process has not been fully understood yet. Here, we show that phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) is constitutively active during preimplantation development. Using pharmacological inhibition, we demonstrate that PI3K/AKT enables the formation of a functional ICM capable of giving rise to both the Epi and the PrE: it maintains the expression of the TF NANOG, which specifies the Epi, and confers responsiveness to FGF4, which is essential for PrE specification. Our work thus identifies PI3K/AKT signaling as an upstream regulator controlling the molecular events required for both Epi and PrE specification.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"144 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489626","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
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