Pub Date : 2025-03-07DOI: 10.1016/j.devcel.2025.02.008
Ulf Tiemann, Chenglei Tian, Florian Hermann, Martin Proks, Emilie Skovgaard, Ivan Kulik, Yilin Di, Jakub Sedzinski, Henrik Semb
A central question in cell and developmental biology is how extracellular cues control the differentiation of multipotent progenitors in a dynamically changing niche. Here, we identify apical-basal polarity as the main regulator of the differentiation of multipotent pancreatic Neurogenin3+ endocrine progenitors (EPs) into the beta or alpha cell fates. We show that human EPs dynamically change their apical-basal polarity status. Whereas polarized EPs are predisposed to differentiate into beta cells rather than alpha cells, inhibiting apical-basal polarity selectively suppresses beta cell differentiation. Single-cell RNA sequencing and complementary mechanistic data demonstrate that apical-basal polarity in human EPs promotes beta cell specification via cyclic AMP (cAMP)/PKA-cAMP response element binding protein (CREB)-EGR1-mediated inhibition of ARX expression, while reduced cAMP levels in non-polarized human EPs maintain expression of ARX, leading to alpha cell differentiation. These findings identify the apical-basal polarity status of multipotent EPs as a critical epithelial feature that determines their fate into the alpha or beta cell lineages.
{"title":"Pancreatic alpha and beta cell fate choice is directed by apical-basal polarity dynamics","authors":"Ulf Tiemann, Chenglei Tian, Florian Hermann, Martin Proks, Emilie Skovgaard, Ivan Kulik, Yilin Di, Jakub Sedzinski, Henrik Semb","doi":"10.1016/j.devcel.2025.02.008","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.02.008","url":null,"abstract":"A central question in cell and developmental biology is how extracellular cues control the differentiation of multipotent progenitors in a dynamically changing niche. Here, we identify apical-basal polarity as the main regulator of the differentiation of multipotent pancreatic Neurogenin3<sup>+</sup> endocrine progenitors (EPs) into the beta or alpha cell fates. We show that human EPs dynamically change their apical-basal polarity status. Whereas polarized EPs are predisposed to differentiate into beta cells rather than alpha cells, inhibiting apical-basal polarity selectively suppresses beta cell differentiation. Single-cell RNA sequencing and complementary mechanistic data demonstrate that apical-basal polarity in human EPs promotes beta cell specification via cyclic AMP (cAMP)/PKA-cAMP response element binding protein (CREB)-EGR1-mediated inhibition of ARX expression, while reduced cAMP levels in non-polarized human EPs maintain expression of ARX, leading to alpha cell differentiation. These findings identify the apical-basal polarity status of multipotent EPs as a critical epithelial feature that determines their fate into the alpha or beta cell lineages.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"29 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569567","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}
Pub Date : 2025-03-05DOI: 10.1016/j.devcel.2025.02.006
Yuki Hata, Nicola Hetherington, Kai Battenberg, Atsuko Hirota, Aki Minoda, Makoto Hayashi, Junko Kyozuka
The shoot apical meristem (SAM), which contains pluripotent stem cells, serves as the source of the entire shoot system in land plants. To find the mechanisms underlying SAM development and its origin, we employed single-nucleus RNA sequencing technology in Physcomitrium patens, which contains a single stem cell known as the gametophore apical cell. We identified distinct cell clusters representing major cell types of the P. patens gametophyte, including the gametophore apical cells. We showed dynamic gene expression changes during cell fate progression in the gametophore apical cell and found upregulation of cytokinin biosynthesis genes in this cell. We also identified ENHANCER OF SHOOT REGENERATION 1 (ESR1) orthologs as important regulators of gametophore apical cells downstream of cytokinin. Given that ESRs promote SAM formation under cytokinin in angiosperms, we propose that the cytokinin-ESR module represents a conserved mechanism promoting stem cell identity that evolved in the common ancestor of land plants.
{"title":"snRNA-seq analysis of the moss Physcomitrium patens identifies a conserved cytokinin-ESR module promoting pluripotent stem cell identity","authors":"Yuki Hata, Nicola Hetherington, Kai Battenberg, Atsuko Hirota, Aki Minoda, Makoto Hayashi, Junko Kyozuka","doi":"10.1016/j.devcel.2025.02.006","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.02.006","url":null,"abstract":"The shoot apical meristem (SAM), which contains pluripotent stem cells, serves as the source of the entire shoot system in land plants. To find the mechanisms underlying SAM development and its origin, we employed single-nucleus RNA sequencing technology in <em>Physcomitrium patens</em>, which contains a single stem cell known as the gametophore apical cell. We identified distinct cell clusters representing major cell types of the <em>P. patens</em> gametophyte, including the gametophore apical cells. We showed dynamic gene expression changes during cell fate progression in the gametophore apical cell and found upregulation of cytokinin biosynthesis genes in this cell. We also identified <em>ENHANCER OF SHOOT REGENERATION 1</em> (<em>ESR1</em>) orthologs as important regulators of gametophore apical cells downstream of cytokinin. Given that ESRs promote SAM formation under cytokinin in angiosperms, we propose that the cytokinin-ESR module represents a conserved mechanism promoting stem cell identity that evolved in the common ancestor of land plants.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"1 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546533","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}
Pub Date : 2025-02-27DOI: 10.1016/j.devcel.2025.02.001
Nora Haacke, Hui Wang, Shu Yan, Marko Barovic, Xiaofei Li, Kosuke Nagai, Adelina Botezatu, Aikaterini Hatzioannou, Bettina Gercken, Giulia Trimaglio, Anisha U. Shah, Jun Wang, Ling Ye, Mangesh T. Jaykar, Martina Rauner, Ben Wielockx, Kyoung-Jin Chung, Mihai G. Netea, Lydia Kalafati, George Hajishengallis, Triantafyllos Chavakis
We previously demonstrated that long-term trained immunity (TRIM) involves adaptations that imprint innate immune memory in long-lived myelopoiesis precursors and their progeny, monocytes/macrophages and neutrophils, which thereby acquire enhanced responsiveness to future challenges. Here, we show that a distinct component of myeloid biology, osteoclastogenesis, can also undergo innate immune training. Indeed, β-glucan-induced TRIM was associated with an increased osteoclastogenesis bias in the bone marrow and an expansion of monocytes/osteoclast progenitors in the periphery, resulting in aggravated severity of experimental periodontitis and arthritis. In the setting of trained inflammatory osteoclastogenesis, we observed transcriptomic rewiring in synovial myeloid cells of arthritic mice, featuring prominent upregulation of the transcription factor melanogenesis-associated transcription factor (MITF). Adoptive transfer of splenic monocytes from β-glucan-trained mice to naive recipients exacerbated arthritis in the latter in a strictly MITF-dependent manner. Our findings establish trained osteoclastogenesis as a maladaptive component of TRIM and potentially provide therapeutic targets in inflammatory bone loss disorders.
我们之前证明，长期训练免疫（TRIM）涉及在长寿命骨髓前体及其后代（单核细胞/巨噬细胞和中性粒细胞）中印刻先天性免疫记忆的适应性，从而增强对未来挑战的反应能力。在这里，我们展示了髓细胞生物学的一个独特组成部分--破骨细胞生成也可以接受先天性免疫训练。事实上，β-葡聚糖诱导的 TRIM 与骨髓中破骨细胞生成偏倚的增加和外周单核细胞/破骨细胞祖细胞的扩增有关，导致实验性牙周炎和关节炎的严重程度加剧。在训练有素的炎症性破骨细胞生成的背景下，我们观察到关节炎小鼠滑膜髓系细胞的转录组重构，其特点是转录因子黑色素生成相关转录因子（MITF）的显著上调。将经过β-葡聚糖训练的小鼠脾脏单核细胞收养性转移给天真受体，会以严格的MITF依赖性方式加重后者的关节炎。我们的研究结果表明，训练有素的破骨细胞生成是 TRIM 的不良适应成分，有可能为炎症性骨质流失疾病提供治疗靶点。
{"title":"Innate immune training of osteoclastogenesis promotes inflammatory bone loss in mice","authors":"Nora Haacke, Hui Wang, Shu Yan, Marko Barovic, Xiaofei Li, Kosuke Nagai, Adelina Botezatu, Aikaterini Hatzioannou, Bettina Gercken, Giulia Trimaglio, Anisha U. Shah, Jun Wang, Ling Ye, Mangesh T. Jaykar, Martina Rauner, Ben Wielockx, Kyoung-Jin Chung, Mihai G. Netea, Lydia Kalafati, George Hajishengallis, Triantafyllos Chavakis","doi":"10.1016/j.devcel.2025.02.001","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.02.001","url":null,"abstract":"We previously demonstrated that long-term trained immunity (TRIM) involves adaptations that imprint innate immune memory in long-lived myelopoiesis precursors and their progeny, monocytes/macrophages and neutrophils, which thereby acquire enhanced responsiveness to future challenges. Here, we show that a distinct component of myeloid biology, osteoclastogenesis, can also undergo innate immune training. Indeed, β-glucan-induced TRIM was associated with an increased osteoclastogenesis bias in the bone marrow and an expansion of monocytes/osteoclast progenitors in the periphery, resulting in aggravated severity of experimental periodontitis and arthritis. In the setting of trained inflammatory osteoclastogenesis, we observed transcriptomic rewiring in synovial myeloid cells of arthritic mice, featuring prominent upregulation of the transcription factor melanogenesis-associated transcription factor (MITF). Adoptive transfer of splenic monocytes from β-glucan-trained mice to naive recipients exacerbated arthritis in the latter in a strictly MITF-dependent manner. Our findings establish trained osteoclastogenesis as a maladaptive component of TRIM and potentially provide therapeutic targets in inflammatory bone loss disorders.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"19 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506856","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}
Pub Date : 2025-02-27DOI: 10.1016/j.devcel.2025.02.003
Hiroshi Takagi, Nayoung Lee, Andrew K. Hempton, Savita Purushwani, Michitaka Notaguchi, Kota Yamauchi, Kazumasa Shirai, Yaichi Kawakatsu, Susumu Uehara, William G. Albers, Benjamin L.R. Downing, Shogo Ito, Takamasa Suzuki, Takakazu Matsuura, Izumi C. Mori, Nobutaka Mitsuda, Daisuke Kurihara, Tomonao Matsushita, Young Hun Song, Yoshikatsu Sato, Takato Imaizumi
Plants induce the expression of the florigen FLOWERING LOCUS T (FT) in response to seasonal changes. FT is expressed in a distinct subset of phloem companion cells in Arabidopsis. Using tissue-specific translatome analysis, we discovered that the FT-expressing cells also express FLOWERING PROMOTING FACTOR 1 (FPF1)-LIKE PROTEIN 1 (FLP1), specifically under long-day conditions with the red/far-red ratio of natural sunlight. The master regulator of FT, CONSTANS (CO), is essential for FLP1 expression, suggesting that FLP1 is involved in the photoperiod pathway. We show that FLP1 promotes early flowering independently of FT, is active in the shoot apical meristem, and induces the expression of SEPALLATA3 (SEP3), a key E-class homeotic gene. Unlike FT, FLP1 also facilitates inflorescence stem elongation. Our cumulative evidence suggests that the small FLP1 protein acts as a mobile signal like FT. Taken together, FLP1 accelerates flowering in parallel with FT and orchestrates flowering and stem elongation during the reproductive transition.
{"title":"Florigen-producing cells express FPF1-LIKE PROTEIN 1 to accelerate flowering and stem growth in Arabidopsis","authors":"Hiroshi Takagi, Nayoung Lee, Andrew K. Hempton, Savita Purushwani, Michitaka Notaguchi, Kota Yamauchi, Kazumasa Shirai, Yaichi Kawakatsu, Susumu Uehara, William G. Albers, Benjamin L.R. Downing, Shogo Ito, Takamasa Suzuki, Takakazu Matsuura, Izumi C. Mori, Nobutaka Mitsuda, Daisuke Kurihara, Tomonao Matsushita, Young Hun Song, Yoshikatsu Sato, Takato Imaizumi","doi":"10.1016/j.devcel.2025.02.003","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.02.003","url":null,"abstract":"Plants induce the expression of the florigen FLOWERING LOCUS T (FT) in response to seasonal changes. <em>FT</em> is expressed in a distinct subset of phloem companion cells in <em>Arabidopsis</em>. Using tissue-specific translatome analysis, we discovered that the <em>FT</em>-expressing cells also express <em>FLOWERING PROMOTING FACTOR 1</em> (<em>FPF1</em>)<em>-LIKE PROTEIN 1</em> (<em>FLP1</em>), specifically under long-day conditions with the red/far-red ratio of natural sunlight. The master regulator of <em>FT</em>, CONSTANS (CO), is essential for <em>FLP1</em> expression, suggesting that <em>FLP1</em> is involved in the photoperiod pathway. We show that <em>FLP1</em> promotes early flowering independently of <em>FT</em>, is active in the shoot apical meristem, and induces the expression of <em>SEPALLATA</em><em>3</em> (<em>SEP3</em>), a key E-class homeotic gene. Unlike <em>FT</em>, <em>FLP1</em> also facilitates inflorescence stem elongation. Our cumulative evidence suggests that the small FLP1 protein acts as a mobile signal like FT. Taken together, FLP1 accelerates flowering in parallel with FT and orchestrates flowering and stem elongation during the reproductive transition.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"82 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143507256","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}
Pub Date : 2025-02-26DOI: 10.1016/j.devcel.2025.02.002
Shreeta Chakraborty, Nina Wenzlitschke, Matthew J. Anderson, Ariel Eraso, Manon Baudic, Joyce J. Thompson, Alicia A. Evans, Lilly M. Shatford-Adams, Raj Chari, Parirokh Awasthi, Ryan K. Dale, Mark Lewandoski, Timothy J. Petros, Pedro P. Rocha
Chromatin domains delimited by CTCF can restrict the range of enhancer action. However, disruption of some domain boundaries results in mild gene dysregulation and phenotypes. We tested whether perturbing a domain with multiple developmental regulators would lead to more severe outcomes. We chose a domain with three FGF ligand genes—Fgf3, Fgf4, and Fgf15—that control different murine developmental processes. Heterozygous deletion of a 23.9-kb boundary defined by four CTCF sites led to ectopic interactions of the FGF genes with enhancers active in the brain and induced FGF expression. This caused orofacial clefts, encephalocele, and fully penetrant perinatal lethality. Loss of the single CTCF motif oriented toward the enhancers—but not the three toward the FGF genes—recapitulated these phenotypes. Our works shows that small sequence variants at particular domain boundaries can have a surprisingly outsized effect and must be considered as potential sources of gene dysregulation in development and disease.
{"title":"Deletion of a single CTCF motif at the boundary of a chromatin domain with three FGF genes disrupts gene expression and embryonic development","authors":"Shreeta Chakraborty, Nina Wenzlitschke, Matthew J. Anderson, Ariel Eraso, Manon Baudic, Joyce J. Thompson, Alicia A. Evans, Lilly M. Shatford-Adams, Raj Chari, Parirokh Awasthi, Ryan K. Dale, Mark Lewandoski, Timothy J. Petros, Pedro P. Rocha","doi":"10.1016/j.devcel.2025.02.002","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.02.002","url":null,"abstract":"Chromatin domains delimited by CTCF can restrict the range of enhancer action. However, disruption of some domain boundaries results in mild gene dysregulation and phenotypes. We tested whether perturbing a domain with multiple developmental regulators would lead to more severe outcomes. We chose a domain with three FGF ligand genes—<em>Fgf3</em>, <em>Fgf4</em>, and <em>Fgf15</em>—that control different murine developmental processes. Heterozygous deletion of a 23.9-kb boundary defined by four CTCF sites led to ectopic interactions of the FGF genes with enhancers active in the brain and induced FGF expression. This caused orofacial clefts, encephalocele, and fully penetrant perinatal lethality. Loss of the single CTCF motif oriented toward the enhancers—but not the three toward the FGF genes—recapitulated these phenotypes. Our works shows that small sequence variants at particular domain boundaries can have a surprisingly outsized effect and must be considered as potential sources of gene dysregulation in development and disease.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"6 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495771","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}
Pub Date : 2025-02-24DOI: 10.1016/j.devcel.2025.01.021
Pui Man Low, Que Kong, Leonard Blaschek, Zhiming Ma, Peng Ken Lim, Yuzhou Yang, Trisha Quek, Cuithbert J.R. Lim, Sanjay K. Singh, Christoph Crocoll, Ellen Engquist, Jakob S. Thorsen, Sitakanta Pattanaik, Wan Ting Tee, Marek Mutwil, Yansong Miao, Ling Yuan, Deyang Xu, Staffan Persson, Wei Ma
The plant funiculus anchors the developing seed to the placenta within the inner dorsal pod strands of the silique wall and directly transports nutrients to the seeds. The lignified vasculature critically supports nutrient transport through the funiculus. However, molecular mechanisms underlying lignified secondary cell wall (SCW) biosynthesis in the funiculus remain elusive. Here, we show that the transcription factor ZINC FINGER PROTEIN2 (ZFP2) represses SCW formation in the cortex cells that surround the vasculature. This function is essential for efficient nutrient loading into the seeds. Notably, ZFP2 directly acts on the SCW transcription factor NAC SECONDARY WALL THICKENING PROMOTING FACTOR1 (NST1) to repress cortex cell lignification, providing a mechanism of how SCW biosynthesis is restricted to the vasculature of the funiculus to ensure proper seed loading in Arabidopsis.
{"title":"ZINC FINGER PROTEIN2 suppresses funiculus lignification to ensure seed loading efficiency in Arabidopsis","authors":"Pui Man Low, Que Kong, Leonard Blaschek, Zhiming Ma, Peng Ken Lim, Yuzhou Yang, Trisha Quek, Cuithbert J.R. Lim, Sanjay K. Singh, Christoph Crocoll, Ellen Engquist, Jakob S. Thorsen, Sitakanta Pattanaik, Wan Ting Tee, Marek Mutwil, Yansong Miao, Ling Yuan, Deyang Xu, Staffan Persson, Wei Ma","doi":"10.1016/j.devcel.2025.01.021","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.01.021","url":null,"abstract":"The plant funiculus anchors the developing seed to the placenta within the inner dorsal pod strands of the silique wall and directly transports nutrients to the seeds. The lignified vasculature critically supports nutrient transport through the funiculus. However, molecular mechanisms underlying lignified secondary cell wall (SCW) biosynthesis in the funiculus remain elusive. Here, we show that the transcription factor ZINC FINGER PROTEIN2 (ZFP2) represses SCW formation in the cortex cells that surround the vasculature. This function is essential for efficient nutrient loading into the seeds. Notably, ZFP2 directly acts on the SCW transcription factor <em>NAC SECONDARY WALL THICKENING PROMOTING FACTOR1</em> (<em>NST1</em>) to repress cortex cell lignification, providing a mechanism of how SCW biosynthesis is restricted to the vasculature of the funiculus to ensure proper seed loading in <em>Arabidopsis</em>.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"174 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486522","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}
Pub Date : 2025-02-24DOI: 10.1016/j.devcel.2025.01.019
Natalia Guayazán-Palacios, Adam D. Steinbrenner
Regulation of immunity is critical to balance growth and defense signaling. In this issue of Developmental Cell, Zhou et al. investigate two antagonistic receptors, SYR1 and SYR2, that control the growth-defense trade-off in plants. This work advances our understanding of the plant receptor kinase network in terms of molecular signaling and evolution of a feedback-based regulatory mechanism.
{"title":"Plant cell surface receptors at the forefront of the growth-defense trade-off","authors":"Natalia Guayazán-Palacios, Adam D. Steinbrenner","doi":"10.1016/j.devcel.2025.01.019","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.01.019","url":null,"abstract":"Regulation of immunity is critical to balance growth and defense signaling. In this issue of <em>Developmental Cell</em>, Zhou et al. investigate two antagonistic receptors, SYR1 and SYR2, that control the growth-defense trade-off in plants. This work advances our understanding of the plant receptor kinase network in terms of molecular signaling and evolution of a feedback-based regulatory mechanism.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"4 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477698","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}
Pub Date : 2025-02-24DOI: 10.1016/j.devcel.2025.01.005
Benedetta Artegiani, Delilah Hendriks
Human organoids are a widely used tool in cell biology to study homeostatic processes, disease, and development. The term organoids covers a plethora of model systems from different cellular origins that each have unique features and applications but bring their own challenges. This review discusses the basic principles underlying organoids generated from pluripotent stem cells (PSCs) as well as those derived from tissue stem cells (TSCs). We consider how well PSC- and TSC-organoids mimic the different intended organs in terms of cellular complexity, maturity, functionality, and the ongoing efforts to constitute predictive complex models of in vivo situations. We discuss the advantages and limitations associated with each system to answer different biological questions including in the field of cancer and developmental biology, and with respect to implementing emerging advanced technologies, such as (spatial) -omics analyses, CRISPR screens, and high-content imaging screens. We postulate how the two fields may move forward together, integrating advantages of one to the other.
{"title":"Organoids from pluripotent stem cells and human tissues: When two cultures meet each other","authors":"Benedetta Artegiani, Delilah Hendriks","doi":"10.1016/j.devcel.2025.01.005","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.01.005","url":null,"abstract":"Human organoids are a widely used tool in cell biology to study homeostatic processes, disease, and development. The term organoids covers a plethora of model systems from different cellular origins that each have unique features and applications but bring their own challenges. This review discusses the basic principles underlying organoids generated from pluripotent stem cells (PSCs) as well as those derived from tissue stem cells (TSCs). We consider how well PSC- and TSC-organoids mimic the different intended organs in terms of cellular complexity, maturity, functionality, and the ongoing efforts to constitute predictive complex models of <em>in vivo</em> situations. We discuss the advantages and limitations associated with each system to answer different biological questions including in the field of cancer and developmental biology, and with respect to implementing emerging advanced technologies, such as (spatial) -omics analyses, CRISPR screens, and high-content imaging screens. We postulate how the two fields may move forward together, integrating advantages of one to the other.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"24 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477697","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}
The concept that mechanical cell competition may contribute to tumor cell expansion has been widely discussed. However, whether this process could occur during natural tumor progression, as well as its underlying mechanisms and clinical implications, remains largely unknown. In this study, we observed that self-seeded tumor cell lines of human oral cancer, SCC9- and SCC25-seeded cells, exhibited a mechanical competitive advantage, outcompeted neighboring cells, and became “winner” cells. Mechanical compression-induced calcium influx activates myosin II in “loser” cells, leading to apoptotic nuclear breakdown and subsequent clearance. N-cadherin/Rac1/PAK1/myosin light-chain kinase (MLCK)-controlled myosin II inactivation endows cells with resistance to mechanical stress and superior cellular flexibility, thus providing a cell competition advantage to self-seeded cells. The activation of the N-cadherin/Rac1/PAK1/MLCK/myosin II signaling axis is associated with drug resistance. Together, these results suggest that N-cadherin/Rac1/PAK1/MLCK signaling-induced myosin II inactivation enables tumor cells to acquire resistance to mechanical stress and a competitive advantage. Our study also provides insights into drug resistance from a stress-sensitivity perspective.
{"title":"N-cadherin-triggered myosin II inactivation provides tumor cells with a mechanical cell competition advantage and chemotherapy resistance","authors":"Zhenlin Dai, Shengkai Chen, Jianbo Shi, Mengyu Rui, Qin Xu","doi":"10.1016/j.devcel.2025.01.020","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.01.020","url":null,"abstract":"The concept that mechanical cell competition may contribute to tumor cell expansion has been widely discussed. However, whether this process could occur during natural tumor progression, as well as its underlying mechanisms and clinical implications, remains largely unknown. In this study, we observed that self-seeded tumor cell lines of human oral cancer, SCC9- and SCC25-seeded cells, exhibited a mechanical competitive advantage, outcompeted neighboring cells, and became “winner” cells. Mechanical compression-induced calcium influx activates myosin II in “loser” cells, leading to apoptotic nuclear breakdown and subsequent clearance. N-cadherin/Rac1/PAK1/myosin light-chain kinase (MLCK)-controlled myosin II inactivation endows cells with resistance to mechanical stress and superior cellular flexibility, thus providing a cell competition advantage to self-seeded cells. The activation of the N-cadherin/Rac1/PAK1/MLCK/myosin II signaling axis is associated with drug resistance. Together, these results suggest that N-cadherin/Rac1/PAK1/MLCK signaling-induced myosin II inactivation enables tumor cells to acquire resistance to mechanical stress and a competitive advantage. Our study also provides insights into drug resistance from a stress-sensitivity perspective.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"12 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463090","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}
Pub Date : 2025-02-20DOI: 10.1016/j.devcel.2025.01.018
Megan Rothstein, Ana Paula Azambuja, Tatiane Y. Kanno, Catriona Breen, Marcos Simoes-Costa
The neural crest is a highly plastic stem cell population that represents an exception to the germ layer theory. Despite being of ectodermal origin, cranial neural crest cells can differentiate into skeletal derivatives typically formed by mesoderm. Here, we report that SMAD2/3-mediated transforming growth factor β (TGF-β) signaling enhances neural crest developmental potential in the chicken embryo. Our results show that TGF-β signaling modulates neural crest axial identity and directly controls the gene circuits that support skeletal differentiation. Cooperation between TGF-β and low levels of WNT signaling in the embryonic head activates cranial-specific cis-regulatory elements. Activation of TGF-β signaling reprogrammed trunk neural crest cells into adopting an anterior identity and led to the development of an improved protocol for the generation of human cranial neural crest cells. Our findings indicate TGF-β signaling is required for the specification of cranial neural crest cells, endowing them with the potential to give rise to the craniofacial skeleton.
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