Developmental cell最新文献

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A single-cell transcriptomic census of mammalian olfactory epithelium aging 哺乳动物嗅上皮细胞老化的单细胞转录组普查
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-08-21 DOI: 10.1016/j.devcel.2024.07.020
Weihao Li, Tingting Wu, Kesen Zhu, Guangyi Ba, Jinxia Liu, Ping Zhou, Shengjv Li, Li Wang, Huanhai Liu, Wenwen Ren, Hongmeng Yu, Yiqun Yu
{"title":"A single-cell transcriptomic census of mammalian olfactory epithelium aging","authors":"Weihao Li, Tingting Wu, Kesen Zhu, Guangyi Ba, Jinxia Liu, Ping Zhou, Shengjv Li, Li Wang, Huanhai Liu, Wenwen Ren, Hongmeng Yu, Yiqun Yu","doi":"10.1016/j.devcel.2024.07.020","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.07.020","url":null,"abstract":"<p>Mammalian olfactory epithelium has the capacity of self-renewal throughout life. Aging is one of the major causes leading to the olfactory dysfunction. Here, we performed single-cell RNA sequencing (scRNA-seq) analysis on young and aged murine olfactory epithelium (OE) and identified aging-related differentially expressed genes (DEGs) throughout 21 cell types. Aging led to the presence of activated horizontal basal cells (HBCs) in the OE and promoted cellular interaction between HBCs and neutrophils. Aging enhanced the expression of Egr1 and Fos in sustentacular cell differentiation from multipotent progenitors, whereas Bcl11b was downregulated during the sensory neuronal homeostasis in the aged OE. Egr1 and Cebpb were predictive core regulatory factors of the transcriptional network in the OE. Overexpression of Egr1 in aged OE organoids promoted cell proliferation and neuronal differentiation. Moreover, aging altered expression levels and frequencies of olfactory receptors. These findings provide a cellular and molecular framework of OE aging at the single-cell resolution.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142023078","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
Identifying FUS amyotrophic lateral sclerosis disease signatures in patient dermal fibroblasts. 识别患者真皮成纤维细胞中的 FUS 肌萎缩侧索硬化症疾病特征。
IF 10.7 1区 生物学
Developmental cell Pub Date : 2024-08-19 Epub Date: 2024-06-14 DOI: 10.1016/j.devcel.2024.05.011
Karl Kumbier, Maike Roth, Zizheng Li, Julia Lazzari-Dean, Christopher Waters, Sabrina Hammerlindl, Capria Rinaldi, Ping Huang, Vladislav A Korobeynikov, Hemali Phatnani, Neil Shneider, Matthew P Jacobson, Lani F Wu, Steven J Altschuler
{"title":"Identifying FUS amyotrophic lateral sclerosis disease signatures in patient dermal fibroblasts.","authors":"Karl Kumbier, Maike Roth, Zizheng Li, Julia Lazzari-Dean, Christopher Waters, Sabrina Hammerlindl, Capria Rinaldi, Ping Huang, Vladislav A Korobeynikov, Hemali Phatnani, Neil Shneider, Matthew P Jacobson, Lani F Wu, Steven J Altschuler","doi":"10.1016/j.devcel.2024.05.011","DOIUrl":"10.1016/j.devcel.2024.05.011","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, highly heterogeneous neurodegenerative disease, underscoring the importance of obtaining information to personalize clinical decisions quickly after diagnosis. Here, we investigated whether ALS-relevant signatures can be detected directly from biopsied patient fibroblasts. We profiled familial ALS (fALS) fibroblasts, representing a range of mutations in the fused in sarcoma (FUS) gene and ages of onset. To differentiate FUS fALS and healthy control fibroblasts, machine-learning classifiers were trained separately on high-content imaging and transcriptional profiles. \"Molecular ALS phenotype\" scores, derived from these classifiers, captured a spectrum from disease to health. Interestingly, these scores negatively correlated with age of onset, identified several pre-symptomatic individuals and sporadic ALS (sALS) patients with FUS-like fibroblasts, and quantified \"movement\" of FUS fALS and \"FUS-like\" sALS toward health upon FUS ASO treatment. Taken together, these findings provide evidence that non-neuronal patient fibroblasts can be used for rapid, personalized assessment in ALS.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327375","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
Developmental control of rod number via a light-dependent retrograde pathway from intrinsically photosensitive retinal ganglion cells 通过来自固有光敏视网膜神经节细胞的光依赖性逆行途径控制视杆细胞数量的发育
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-08-13 DOI: 10.1016/j.devcel.2024.07.018
{"title":"Developmental control of rod number via a light-dependent retrograde pathway from intrinsically photosensitive retinal ganglion cells","authors":"","doi":"10.1016/j.devcel.2024.07.018","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.07.018","url":null,"abstract":"<p>Photoreception is essential for the development of the visual system, shaping vision’s first synapse to cortical development. Here, we find that the lighting environment controls developmental rod apoptosis via Opn4-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs). Using genetics, sensory environment manipulations, and computational approaches, we establish a pathway where light-dependent glutamate released from ipRGCs is detected via a transiently expressed glutamate receptor (Grik3) on rod precursors within the inner retina. Communication between these cells is mediated by hybrid neurites on ipRGCs that sense light before eye opening. These structures span the ipRGC-rod precursor distance over development and contain the machinery for photoreception (Opn4) and neurotransmitter release (Vglut2 &amp; Syp). Assessment of the human gestational retina identifies conserved hallmarks of an ipRGC-to-rod axis, including displaced rod precursors, transient <em>GRIK3</em> expression, and ipRGCs with deep-projecting neurites. This analysis defines an adaptive retrograde pathway linking the sensory environment to rod precursors via ipRGCs prior to eye opening.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974186","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
Tight junctions control lumen morphology via hydrostatic pressure and junctional tension 紧密连接通过静水压力和连接张力控制管腔形态
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-08-12 DOI: 10.1016/j.devcel.2024.07.016
{"title":"Tight junctions control lumen morphology via hydrostatic pressure and junctional tension","authors":"","doi":"10.1016/j.devcel.2024.07.016","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.07.016","url":null,"abstract":"<p>Formation of fluid-filled lumina by epithelial tissues is essential for organ development. How cells control the hydraulic and cortical forces to control lumen morphology is not well understood. Here, we quantified the mechanical role of tight junctions in lumen formation using MDCK-II cysts. We found that the paracellular ion barrier formed by claudin receptors is not required for the hydraulic inflation of a lumen. However, the depletion of the zonula occludens scaffold resulted in lumen collapse and folding of apical membranes. Combining quantitative measurements of hydrostatic lumen pressure and junctional tension with modeling enabled us to explain lumen morphologies from the pressure-tension force balance. Tight junctions promote lumen inflation by decreasing cortical tension via the inhibition of myosin. In addition, our results suggest that excess apical area contributes to lumen opening. Overall, we provide a mechanical understanding of how epithelial cells use tight junctions to modulate tissue and lumen shape.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918681","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
Prior Fc receptor activation primes macrophages for increased sensitivity to IgG via long-term and short-term mechanisms 事先激活 Fc 受体可通过长期和短期机制使巨噬细胞对 IgG 的敏感性增强
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-08-12 DOI: 10.1016/j.devcel.2024.07.017
{"title":"Prior Fc receptor activation primes macrophages for increased sensitivity to IgG via long-term and short-term mechanisms","authors":"","doi":"10.1016/j.devcel.2024.07.017","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.07.017","url":null,"abstract":"<p>Macrophages measure the “eat-me” signal immunoglobulin G (IgG) to identify targets for phagocytosis. We tested whether prior encounters with IgG influence macrophage appetite. IgG is recognized by the Fc receptor. To temporally control Fc receptor activation, we engineered an Fc receptor that is activated by the light-induced oligomerization of Cry2, triggering phagocytosis. Using this tool, we demonstrate that subthreshold Fc receptor activation primes mouse bone-marrow-derived macrophages to be more sensitive to IgG in future encounters. Macrophages that have previously experienced subthreshold Fc receptor activation eat more IgG-bound human cancer cells. Increased phagocytosis occurs by two discrete mechanisms—a short- and long-term priming. Long-term priming requires new protein synthesis and Erk activity. Short-term priming does not require new protein synthesis and correlates with an increase in Fc receptor mobility. Our work demonstrates that IgG primes macrophages for increased phagocytosis, suggesting that therapeutic antibodies may become more effective after initial priming doses.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918672","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 analyses identify shared and divergent features of human and mouse kidney development 单细胞比较分析确定了人类和小鼠肾脏发育的共同特征和差异特征
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-08-08 DOI: 10.1016/j.devcel.2024.07.013
{"title":"Comparative single-cell analyses identify shared and divergent features of human and mouse kidney development","authors":"","doi":"10.1016/j.devcel.2024.07.013","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.07.013","url":null,"abstract":"<p>The mammalian kidney maintains fluid homeostasis through diverse epithelial cell types generated from nephron and ureteric progenitor cells. To extend a developmental understanding of the kidney’s epithelial networks, we compared chromatin organization (single-nuclear assay for transposase-accessible chromatin sequencing [ATAC-seq]; 112,864 nuclei) and gene expression (single-cell/nuclear RNA sequencing [RNA-seq]; 109,477 cells/nuclei) in the developing human (10.6–17.6 weeks; <em>n</em> = 10) and mouse (post-natal day [P]0; <em>n</em> = 10) kidney, supplementing analysis with published mouse datasets from earlier stages. Single-cell/nuclear datasets were analyzed at a species level, and then nephron and ureteric cellular lineages were extracted and integrated into a common, cross-species, multimodal dataset. Comparative computational analyses identified conserved and divergent features of chromatin organization and linked gene activity, identifying species-specific and cell-type-specific regulatory programs. <em>In situ</em> validation of human-enriched gene activity points to human-specific signaling interactions in kidney development. Further, human-specific enhancer regions were linked to kidney diseases through genome-wide association studies (GWASs), highlighting the potential for clinical insight from developmental modeling.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141904171","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
GLUD1 determines murine muscle stem cell fate by controlling mitochondrial glutamate levels GLUD1 通过控制线粒体谷氨酸水平决定小鼠肌肉干细胞的命运
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-08-08 DOI: 10.1016/j.devcel.2024.07.015
{"title":"GLUD1 determines murine muscle stem cell fate by controlling mitochondrial glutamate levels","authors":"","doi":"10.1016/j.devcel.2024.07.015","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.07.015","url":null,"abstract":"<p>Muscle stem cells (MuSCs) enable muscle growth and regeneration after exercise or injury, but how metabolism controls their regenerative potential is poorly understood. We describe that primary metabolic changes can determine murine MuSC fate decisions. We found that glutamine anaplerosis into the tricarboxylic acid (TCA) cycle decreases during MuSC differentiation and coincides with decreased expression of the mitochondrial glutamate deaminase GLUD1. Deletion of <em>Glud1</em> in proliferating MuSCs resulted in precocious differentiation and fusion, combined with loss of self-renewal <em>in vitro</em> and <em>in vivo</em>. Mechanistically, deleting <em>Glud1</em> caused mitochondrial glutamate accumulation and inhibited the malate-aspartate shuttle (MAS). The resulting defect in transporting NADH-reducing equivalents into the mitochondria induced compartment-specific NAD<sup>+</sup>/NADH ratio shifts. MAS activity restoration or directly altering NAD<sup>+</sup>/NADH ratios normalized myogenesis. In conclusion, GLUD1 prevents deleterious mitochondrial glutamate accumulation and inactivation of the MAS in proliferating MuSCs. It thereby acts as a compartment-specific metabolic brake on MuSC differentiation.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141904172","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
Itaconate uptake via SLC13A3 improves hepatic antibacterial innate immunity 通过 SLC13A3 吸收伊他康酸可提高肝脏的先天性抗菌免疫能力
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-08-07 DOI: 10.1016/j.devcel.2024.07.011
{"title":"Itaconate uptake via SLC13A3 improves hepatic antibacterial innate immunity","authors":"","doi":"10.1016/j.devcel.2024.07.011","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.07.011","url":null,"abstract":"<p>Itaconate is an immunoregulatory metabolite produced by the mitochondrial enzyme immune-responsive gene 1 (IRG1) in inflammatory macrophages. We recently identified an important mechanism by which itaconate is released from inflammatory macrophages. However, it remains unknown whether extracellular itaconate is taken up by non-myeloid cells to exert immunoregulatory functions. Here, we used a custom-designed CRISPR screen to identify the dicarboxylate transporter solute carrier family 13 member 3 (SLC13A3) as an itaconate importer and to characterize the role of SLC13A3 in itaconate-improved hepatic antibacterial innate immunity. Functionally, liver-specific deletion of <em>Slc13a3</em> impairs hepatic antibacterial innate immunity <em>in vivo</em> and <em>in vitro</em>. Mechanistically, itaconate uptake via SLC13A3 induces transcription factor EB (TFEB)-dependent lysosomal biogenesis and subsequently improves antibacterial innate immunity in mouse hepatocytes. These findings identify SLC13A3 as a key itaconate importer in mouse hepatocytes and will aid in the development of potent itaconate-based antibacterial therapeutics.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899884","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
Hox gene activity directs physical forces to differentially shape chick small and large intestinal epithelia Hox 基因活动引导物理力对雏鸡小肠和大肠上皮进行不同的塑造
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-08-07 DOI: 10.1016/j.devcel.2024.07.012
{"title":"Hox gene activity directs physical forces to differentially shape chick small and large intestinal epithelia","authors":"","doi":"10.1016/j.devcel.2024.07.012","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.07.012","url":null,"abstract":"<p>Hox transcription factors play crucial roles in organizing developmental patterning across metazoa, but how these factors trigger regional morphogenesis has largely remained a mystery. In the developing gut, Hox genes help demarcate identities of intestinal subregions early in embryogenesis, which ultimately leads to their specialization in both form and function. Although the midgut forms villi, the hindgut develops sulci that resolve into heterogeneous outgrowths. Combining mechanical measurements of the embryonic chick intestine and mathematical modeling, we demonstrate that the posterior Hox gene <em>HOXD13</em> regulates biophysical phenomena that shape the hindgut lumen. We further show that HOXD13 acts through the transforming growth factor β (TGF-β) pathway to thicken, stiffen, and promote isotropic growth of the subepithelial mesenchyme—together, these features lead to hindgut-specific surface buckling. TGF-β, in turn, promotes collagen deposition to affect mesenchymal geometry and growth. We thus identify a cascade of events downstream of positional identity that direct posterior intestinal morphogenesis.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899890","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 condensates-to-VPS41-associated phagic vacuoles conversion pathway controls autophagy degradation in plants 凝结物到 VPS41 相关吞噬泡的转化途径控制植物的自噬降解
IF 11.8 1区 生物学
Developmental cell Pub Date : 2024-08-06 DOI: 10.1016/j.devcel.2024.07.010
{"title":"A condensates-to-VPS41-associated phagic vacuoles conversion pathway controls autophagy degradation in plants","authors":"","doi":"10.1016/j.devcel.2024.07.010","DOIUrl":"https://doi.org/10.1016/j.devcel.2024.07.010","url":null,"abstract":"<p>Autophagy is a universal degradation system in eukaryotic cells. In plants, although autophagosome biogenesis has been extensively studied, the mechanism of how autophagosomes are transported to the vacuole for degradation remains largely unexplored. In this study, we demonstrated that upon autophagy induction, <em>Arabidopsis</em> homotypic fusion and protein sorting (HOPS) subunit VPS41 converts first from condensates to puncta, then to ring-like structures, termed VPS41-associated phagic vacuoles (VAPVs), which enclose autophagy-related gene (ATG)8s for vacuolar degradation. This process is initiated by ADP ribosylation factor (ARF)-like GTPases ARLA1s and occurs concurrently with autophagy progression through coupling with the synaptic-soluble N-ethylmaleimide-sensitive factor attachment protein rmleceptor (SNARE) proteins. Unlike in other eukaryotes, autophagy degradation in <em>Arabidopsis</em> is largely independent of the RAB7 pathway. By contrast, dysfunction in the condensates-to-VAPVs conversion process impairs autophagosome structure and disrupts their vacuolar transport, leading to a significant reduction in autophagic flux and plant survival rate. Our findings suggest that the conversion pathway might be an integral part of the autophagy program unique to plants.</p>","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899898","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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