{"title":"Gossiping about death: Apoptosis-induced ERK waves as coordinators of multicellular fate decisions","authors":"Paolo Armando Gagliardi , Olivier Pertz","doi":"10.1016/j.semcdb.2025.103615","DOIUrl":"10.1016/j.semcdb.2025.103615","url":null,"abstract":"<div><div>Apoptosis is now recognized as a highly dynamic process that involves the release of a large set of signaling molecules that convey information to cells neighboring an apoptotic site. Recent studies in epithelial systems have discovered that apoptotic cells trigger waves of pulses of mitogen-activated protein kinase (MAPK) / extracellular signal-regulated kinase (ERK) pathway activity in their neighbors. At the single-cell level, the ERK pulses emerge from the MAPK pathway's excitable network properties, such as ultrasensitivity and adaptation. At the cell population level, apoptosis-induced ERK waves (AiEWs) emerge from propagation of ERK pulses across cells via a mechanism that involves mechanical inputs and paracrine signaling. AiEWs enable cell populations to dynamically coordinate fate decision signaling during tissue homeostasis and development. This spatio-temporal signaling mechanism can be hijacked by cancer cells to induce drug-tolerant persister states when apoptosis is triggered by cytotoxic or targeted therapies, undermining treatment efficacy. In this review, we summarize our current understanding of AiEWs, including their initiation, propagation, and coordination of fate decision signaling within a population. We discuss how the relatively simple properties of single cells, and their interactions within a collective coordinate these dynamic signaling patterns. We highlight their implication in resistance to cancer therapy and explore potential strategies to target these waves to re-sensitize cancer cells. Finally, we discuss emerging technologies and future directions to expand the study of this biological phenomenon.</div></div>","PeriodicalId":21735,"journal":{"name":"Seminars in cell & developmental biology","volume":"171 ","pages":"Article 103615"},"PeriodicalIF":6.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A near death experience: The secret stem cell life of caspase-3","authors":"Mahasen Sarji , Roi Ankawa , Matan Yampolsky , Yaron Fuchs","doi":"10.1016/j.semcdb.2025.103617","DOIUrl":"10.1016/j.semcdb.2025.103617","url":null,"abstract":"<div><div>Caspase-3 is known to play a pivotal role in mediating apoptosis, a key programmed cell death pathway. While extensive research has focused on understanding how caspase-3 is activated and functions during apoptosis, emerging evidence has revealed its significant non-apoptotic roles across various cell types, including stem cells. This review explores the critical involvement of caspase-3 in regulating stem cell properties, maintaining stem cell populations, and facilitating tissue regeneration. We also explore the potential pathological consequences of caspase-3 dysfunction in stem cells and cancer cells alongside the therapeutic opportunities of targeting caspase-3.</div></div>","PeriodicalId":21735,"journal":{"name":"Seminars in cell & developmental biology","volume":"171 ","pages":"Article 103617"},"PeriodicalIF":6.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Timothy C. Byatt , Ehsan Razaghi , Selin Tüzüner , Filipa C. Simões
{"title":"Immune-mediated cardiac development and regeneration","authors":"Timothy C. Byatt , Ehsan Razaghi , Selin Tüzüner , Filipa C. Simões","doi":"10.1016/j.semcdb.2025.103613","DOIUrl":"10.1016/j.semcdb.2025.103613","url":null,"abstract":"<div><div>The complex interplay between the immune and cardiovascular systems during development, homeostasis and regeneration represents a rapidly evolving field in cardiac biology. Single cell technologies, spatial mapping and computational analysis have revolutionised our understanding of the diversity and functional specialisation of immune cells within the heart. From the earliest stages of cardiogenesis, where primitive macrophages guide heart tube formation, to the complex choreography of inflammation and its resolution during regeneration, immune cells emerge as central orchestrators of cardiac fate. Translating these fundamental insights into clinical applications represents a major challenge and opportunity for the field. In this Review, we decode the immunological blueprint of heart development and regeneration to transform cardiovascular disease treatment and unlock the regenerative capacity of the human heart.</div></div>","PeriodicalId":21735,"journal":{"name":"Seminars in cell & developmental biology","volume":"171 ","pages":"Article 103613"},"PeriodicalIF":6.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Why some hearts heal and others don’t: The phylogenetic landscape of cardiac regenerative capacity","authors":"Makoto Nakamura , Guo N. Huang","doi":"10.1016/j.semcdb.2025.103609","DOIUrl":"10.1016/j.semcdb.2025.103609","url":null,"abstract":"<div><div>The limited ability of adult humans to replenish lost heart muscle cells after a heart attack has attracted scientists to explore natural heart regeneration capabilities in the animal kingdom. In particular, research has accelerated since the landmark discovery more than twenty years ago that zebrafish can completely regrow myocardial tissue. In this review, we survey heart regeneration studies in diverse model and non-model animals, aiming to gain insights into both the evolutionary trends in cardiac regenerative potential and the variations among closely related species. Differences in cardiomyogenesis, vasculature formation, and the communication between cardiovascular cells and other players have been investigated to understand the cellular basis, although the precise molecular and genetic causes underlying the stark differences in cardiac regenerative potential among certain close cousins remain largely unknown. By studying cardiovascular regeneration and repair in diverse organisms, we may uncover distinct mechanisms, offering new perspectives for advancing regenerative medicine.</div></div>","PeriodicalId":21735,"journal":{"name":"Seminars in cell & developmental biology","volume":"170 ","pages":"Article 103609"},"PeriodicalIF":6.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanical force-driven cell competition ensures robust morphogen gradient formation","authors":"Kana Aoki , Tohru Ishitani","doi":"10.1016/j.semcdb.2025.103607","DOIUrl":"10.1016/j.semcdb.2025.103607","url":null,"abstract":"<div><div>Morphogen gradients provide positional data and maintain tissue patterns by instructing cells to adopt distinct fates. In contrast, morphogen gradient-forming tissues undergo dynamic morphogenetic movements that generate mechanical forces and can disturb morphogen signal transduction. However, the interactions between morphogen gradients and these forces remain largely unknown. In this study, we described how mechanical force-mediated cell competition corrects noisy morphogen gradients to ensure robust tissue patterns. The Wnt/β-catenin morphogen gradient—that patterns the embryonic anterior-posterior axis—generates cadherin-actomyosin interaction-mediated intercellular tension gradients—termed mechano-gradients. Naturally generated unfit cells that produce noisy Wnt/β-catenin gradients induce local deformation of the mechano-gradients. Neighboring fit cells sense this deformation, resulting in the activation of Piezo family mechanosensitive calcium channels and secretion of annexinA1, which specifically kills unfit cells to recover morphogen gradients. Therefore, mechanical force-mediated cell competition between the morphogen-receiver cells supports robust gradient formation. Additionally, we discuss the potential roles of mechanical force-driven cell competition in other contexts, including organogenesis and cancer.</div></div>","PeriodicalId":21735,"journal":{"name":"Seminars in cell & developmental biology","volume":"170 ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cardiac enhancers: Gateway to the regulatory mechanisms of heart regeneration","authors":"Ian J. Begeman, Megan E. Guyer, Junsu Kang","doi":"10.1016/j.semcdb.2025.103610","DOIUrl":"10.1016/j.semcdb.2025.103610","url":null,"abstract":"<div><div>The adult mammalian heart has limited regenerative capacity. Cardiac injury, such as a myocardial infarction (MI), leads to permanent scarring and impaired heart function. In contrast, neonatal mice and zebrafish possess the ability to repair injured hearts. Cardiac regeneration is driven by profound transcriptional changes, which are controlled by gene regulatory elements, such as tissue regeneration enhancer elements (TREEs). Here, we review recent studies on cardiac injury/regeneration enhancers across species. We further explore regulatory mechanisms governing TREE activities and their associated binding regulators. We also discuss the potential of TREE engineering and how these enhancers can be utilized for heart repair. Decoding the regulatory logic of cardiac regeneration enhancers presents a promising avenue for understanding heart regeneration and advancing therapeutic strategies for heart failure.</div></div>","PeriodicalId":21735,"journal":{"name":"Seminars in cell & developmental biology","volume":"170 ","pages":"Article 103610"},"PeriodicalIF":6.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Emerging roles for microproteins as critical regulators of endoplasmic reticulum function and cellular homeostasis","authors":"Taylor M. Coughlin , Catherine A. Makarewich","doi":"10.1016/j.semcdb.2025.103608","DOIUrl":"10.1016/j.semcdb.2025.103608","url":null,"abstract":"<div><div>The endoplasmic reticulum (ER) is a multifunctional organelle essential for key cellular processes including protein synthesis, calcium homeostasis, and the cellular stress response. It is composed of distinct domains, such as the rough and smooth ER, as well as membrane regions that facilitate direct communication with other organelles, enabling its diverse functions. While many well-characterized ER proteins contribute to these processes, recent studies have revealed a previously underappreciated class of small proteins that play critical regulatory roles. Microproteins, typically under 100 amino acids in length, were historically overlooked due to size-based biases in genome annotation and often misannotated as noncoding RNAs. Advances in ribosome profiling, mass spectrometry, and computational approaches have now enabled the discovery of numerous previously unrecognized microproteins, significantly expanding our understanding of the proteome. While some ER-associated microproteins, such as phospholamban and sarcolipin, were identified decades ago, newly discovered microproteins share similar fundamental characteristics, underscoring the need to refine our understanding of the coding potential of the genome. Molecular studies have demonstrated that ER microproteins play essential roles in calcium regulation, ER stress response, organelle communication, and protein translocation. Moreover, growing evidence suggests that ER microproteins contribute to cellular homeostasis and are implicated in disease processes, including cardiovascular disease and cancer. This review examines the shared and unique functions of ER microproteins, their implications for health and disease, and their potential as therapeutic targets for conditions associated with ER dysfunction.</div></div>","PeriodicalId":21735,"journal":{"name":"Seminars in cell & developmental biology","volume":"170 ","pages":"Article 103608"},"PeriodicalIF":6.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Death fuels growth: Emerging players bridging apoptosis and cell proliferation in Drosophila and beyond","authors":"Caitlin Hounsell, Yun Fan","doi":"10.1016/j.semcdb.2025.103602","DOIUrl":"10.1016/j.semcdb.2025.103602","url":null,"abstract":"<div><div>Tissue homeostasis relies on a delicate balance between cell death and proliferation. Apoptosis plays a key role not only in removing damaged cells but also in promoting tissue recovery through a process known as apoptosis-induced proliferation (AiP). This review highlights how caspases, c-Jun N-terminal Kinase (JNK), and Reactive Oxygen Species (ROS) bridge cell death and proliferation, as revealed through studies using <em>Drosophila</em> as a model organism. We also compare these findings with advances in other model systems and discuss their broader implications for tissue regeneration and tumorigenesis.</div></div>","PeriodicalId":21735,"journal":{"name":"Seminars in cell & developmental biology","volume":"169 ","pages":"Article 103602"},"PeriodicalIF":6.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cilia and flagella – Current understanding and recent advances in divergent experimental systems","authors":"Junmin Pan","doi":"10.1016/j.semcdb.2025.103606","DOIUrl":"10.1016/j.semcdb.2025.103606","url":null,"abstract":"","PeriodicalId":21735,"journal":{"name":"Seminars in cell & developmental biology","volume":"169 ","pages":"Article 103606"},"PeriodicalIF":6.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Geometric factors for cell arrangement: How do cells determine their position in vivo?","authors":"Sungrim Seirin-Lee , Akatsuki Kimura","doi":"10.1016/j.semcdb.2025.103604","DOIUrl":"10.1016/j.semcdb.2025.103604","url":null,"abstract":"<div><div>The spatial arrangement of cells plays a crucial role in ensuring robust development of organisms, directing cells to their specific fates in the right place and at the right time. In early embryogenesis, the cell arrangement is determined by several factors such as the cell division axis, cell-cell interactions, and surrounding geometric constraints. While many species utilize similar principles to determine the cell arrangement, the precise dynamics of cell arrangement differ among species, even at early stages. In particular, geometric constraints significantly impact cell arrangement. Nematode species exhibit diverse cell arrangement dynamics due to their rigid eggshells, which intensively confine the internal cells. In this paper, we review the mechanisms of cell arrangement with a focus on geometric constraints, drawing from interdisciplinary perspectives. We also review mathematical models developed to enhance our understanding of these mechanisms and discuss future directions for theoretical approaches in exploring geometric effects on cell arrangement in various tissues of various species.</div></div>","PeriodicalId":21735,"journal":{"name":"Seminars in cell & developmental biology","volume":"169 ","pages":"Article 103604"},"PeriodicalIF":6.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}