Cells & Development最新文献

{"title":"Blastoid: The future of human development in the laboratory.","authors":"Hyung Kyu Choi, Sung-Hwan Moon","doi":"10.1016/j.cdev.2024.203975","DOIUrl":"10.1016/j.cdev.2024.203975","url":null,"abstract":"<p><p>Research on early human development is crucial for understanding the origins of life and mechanisms underlying disease onset. However, these studies have significant challenges owing to ethical restrictions and technical limitations. Stem cell technology advancement has led to the development of blastoids to overcome these challenges.\" Blastoids are three-dimensional structures produced by pluripotent stem cells (PSCs) that resemble the blastocyst stage of human embryos. Research on blastoids can enhance our understanding of early human development and drive innovations in regenerative medicine and disease modeling. This review outlines the background of blastoid development and highlights the limitations of existing organoid research. It presents developments in blastoid research, from previous studies using animal models to the latest developments using human stem cell-derived blastoids in early human development studies. Additionally, this review provides a comparative analysis of the methods used to develop blastoids across various studies, evaluating their potential as ethical alternatives for regenerative medicine, human developmental biology, and embryonic research. It further assesses the ethical and social considerations surrounding blastoid research, the current strategies to address these concerns, and the potential long-term impact on science and medicine. We aimed to provide a comprehensive understanding of the current trends in blastoid research, offer new insights into early human development, and suggest novel directions and approaches for researchers.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"203975"},"PeriodicalIF":2.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting the mystery of embryonic scaling: The Scalers Hypothesis and its confirmation in sea urchin embryos.","authors":"Polina S Timoshina, Alexey M Nesterenko, Elena A Parshina, Eugeny E Orlov, Fedor M Eroshkin, Andrey G Zaraisky","doi":"10.1016/j.cdev.2024.203972","DOIUrl":"https://doi.org/10.1016/j.cdev.2024.203972","url":null,"abstract":"<p><p>Embryonic scaling, the ability of embryos to regulate their spatial structure in proportion to size, remains a fascinating yet poorly studied problem in developmental biology. First described in sea urchin embryos by Hans Driesch, this phenomenon is now recognized as a striking example of how living organisms use non-equilibrium self-organization, based on reaction-diffusion (RD) systems, to generate pattern-determining morphogen concentration gradients that scale with size. Although specific molecular mechanisms for scaling such gradients have been described in some cases, a general approach for the targeted identification of such mechanisms had not been developed until recently. In search of a solution, we hypothesized the obligatory participation in scaling mechanisms of special genes, which we named \"scalers.\" We supposed that these genes share two critical features: their expression is sensitive to embryo size, and their protein products determine the scale of morphogen concentration gradients. As proof of principle, we recently identified scalers by detecting differentially expressed genes in wild-type and half-size Xenopus laevis gastrula embryos. Furthermore, we described a mechanism by which one of the identified scalers, the gene encoding Metalloproteinase 3 (Mmp3), regulates the scaling of gradients of the morphogenic protein Bmp and its antagonists, Chordin and Noggin1/2. In the present work, we have made an important theoretical generalization of the Scalers Hypothesis by proving a statement regarding the obligatory presence of scalers in closed RD systems generating morphogen concentration gradients. Furthermore, through a systematic analysis of all known types of embryonic scaling models based on RD systems, we demonstrate that scalers are present in all known types of such models, either explicitly or implicitly. Finally, to test the universality of the Scalers Hypothesis, we applied our method to identify scalers that adjust Bmp/Chordin gradients to the size of the sea urchin embryo, Strongylocentrotus droebachiensis. Our results show that at least two members of the gene cluster encoding astacin metalloproteinases of the Span family, namely bp10 and Span, exhibit properties characteristic of scalers. Namely, their expression levels increase significantly in half-size embryos, and their protein products specifically degrade Chordin. Additionally, we found that the loss of function of bp10 and span leads to a narrowing of the dorsal domain of the Bmp signaling nuclear effector, pSmad1/5. These findings not only validate the Scalers Hypothesis but also uncover a novel mechanism by which Span proteinases fine-tune Chordin and Bmp morphogen concentration gradients in sea urchins. Thus, the Scalers Hypothesis and the approach to targeted search for such genes developed on its basis open up promising avenues for future research into scaling mechanisms in various biological systems.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"203972"},"PeriodicalIF":2.1,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Of criminals and cancer: The importance of social bonds and innate morality on cellular societies.","authors":"Anuraag Bukkuri, Frederick R Adler","doi":"10.1016/j.cdev.2024.203964","DOIUrl":"10.1016/j.cdev.2024.203964","url":null,"abstract":"<p><p>The current dogma in cancer biology contends that cancer is an identity problem: mutations in a cell's DNA cause it to \"go rogue\" and proliferate out of control. However, this largely ignores the role of cell-cell interaction and fails to explain phenomena such as cancer reversion, the existence of cancers without mutations, and foreign-body carcinogenesis. In this proof-of-concept paper, we draw on criminology to propose that cancer may alternatively be conceptualized as a relational problem: Although a cell's genetics is essential, the influence of its interaction with other cells is equally important in determining its phenotype. We create a simple agent-based network model of interactions among normal and cancer cells to demonstrate this idea. We find that both high mutation rates and low levels of connectivity among cells can promote oncogenesis. Viewing cancer as a breakdown in communication networks among cells in a tissue complements the gene-centric paradigm nicely and provides a novel perspective for understanding and treating cancer.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"203964"},"PeriodicalIF":2.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"'Three signals - three body axes' as patterning principle in bilaterians.","authors":"Christof Niehrs, Ettore Zapparoli, Hyeyoon Lee","doi":"10.1016/j.cdev.2024.203944","DOIUrl":"10.1016/j.cdev.2024.203944","url":null,"abstract":"<p><p>In vertebrates, the three orthogonal body axes, anteroposterior (AP), dorsoventral (DV) and left-right (LR) are determined at gastrula and neurula stages by the Spemann-Mangold organizer and its equivalents. A common feature of AP and DV axis formation is that an evolutionary conserved interplay between growth factors (Wnt, BMP) and their extracellular antagonists (e.g. Dkk1, Chordin) creates signaling gradients for axial patterning. Recent work showed that LR patterning in Xenopus follows the same principle, with R-spondin 2 (Rspo2) as an extracellular FGF antagonist, which creates a signaling gradient that determines the LR vector. That a triad of anti-FGF, anti-BMP, and anti-Wnt governs LR, DV, and AP axis formation reveals a unifying principle in animal development. We discuss how cross-talk between these three signals confers integrated AP-DV-LR body axis patterning underlying developmental robustness, size scaling, and harmonious regulation. We propose that Urbilateria featured three orthogonal body axes that were governed by a Cartesian coordinate system of orthogonal Wnt/AP, BMP/DV, and FGF/LR signaling gradients.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"203944"},"PeriodicalIF":2.1,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Podoplanin and its multifaceted roles in mammalian developmental program.","authors":"Yi Ying Cheok, Grace Min Yi Tan, Yee Teng Chan, Suhailah Abdullah, Chung Yeng Looi, Won Fen Wong","doi":"10.1016/j.cdev.2024.203943","DOIUrl":"10.1016/j.cdev.2024.203943","url":null,"abstract":"<p><p>Podoplanin is a vital molecule which plays an integral part in the regulation of development, immunity, and cancer. Expression of Podoplanin is detected at different early developmental stages of mammalian embryo, and it functions to modulate morphogenesis of various organ systems. In experimental animal models of different genetic backgrounds, absence of Podoplanin results in either embryonic lethality or immediate death upon birth, suggesting the importance of the gene in early developmental processes. This review discusses the gene and protein structure of Podoplanin; and elucidates various functions of Podoplanin in different systems, including central nervous system as well as respiratory, lymphatic, and cardiovascular systems.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"203943"},"PeriodicalIF":2.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-organization underlies developmental robustness in plants.","authors":"Shuyao Kong, Mingyuan Zhu, Adrienne H K Roeder","doi":"10.1016/j.cdev.2024.203936","DOIUrl":"10.1016/j.cdev.2024.203936","url":null,"abstract":"<p><p>Development is a self-organized process that builds on cells and their interactions. Cells are heterogeneous in gene expression, growth, and division; yet how development is robust despite such heterogeneity is a fascinating question. Here, we review recent progress on this topic, highlighting how developmental robustness is achieved through self-organization. We will first discuss sources of heterogeneity, including stochastic gene expression, heterogeneity in growth rate and direction, and heterogeneity in division rate and precision. We then discuss cellular mechanisms that buffer against such noise, including Paf1C- and miRNA-mediated denoising, spatiotemporal growth averaging and compensation, mechanisms to improve cell division precision, and coordination of growth rate and developmental timing between different parts of an organ. We also discuss cases where such heterogeneity is not buffered but utilized for development. Finally, we highlight potential directions for future studies of noise and developmental robustness.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"203936"},"PeriodicalIF":2.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Head organizer: Cerberus and IGF cooperate in brain induction in Xenopus embryos.","authors":"Yagmur Azbazdar, Edgar M Pera, Edward M De Robertis","doi":"10.1016/j.cdev.2023.203897","DOIUrl":"10.1016/j.cdev.2023.203897","url":null,"abstract":"<p><p>Neural induction by cell-cell signaling was discovered a century ago by the organizer transplantations of Spemann and Mangold in amphibians. Spemann later found that early dorsal blastopore lips induced heads and late organizers trunk-tail structures. Identifying region-specific organizer signals has been a driving force in the progress of animal biology. Head induction in the absence of trunk is designated archencephalic differentiation. Two specific head inducers, Cerberus and Insulin-like growth factors (IGFs), that induce archencephalic brain but not trunk-tail structures have been described previously. However, whether these two signals interact with each other had not been studied to date and was the purpose of the present investigation. It was found that Cerberus, a multivalent growth factor antagonist that inhibits Nodal, BMP and Wnt signals, strongly cooperated with IGF2, a growth factor that provides a positive signal through tyrosine kinase IGF receptors that activate MAPK and other pathways. The ectopic archencephalic structures induced by the combination of Cerberus and IGF2 are of higher frequency and larger than either one alone. They contain brain, a cyclopic eye and multiple olfactory placodes, without trace of trunk structures such as notochord or somites. A dominant-negative secreted IGF receptor 1 blocked Cerberus activity, indicating that endogenous IGF signals are required for ectopic brain formation. In a sensitized embryonic system, in which embryos were depleted of β-catenin, IGF2 did not by itself induce neural tissue while in combination with Cerberus it greatly enhanced formation of circular brain structures expressing the anterior markers Otx2 and Rx2a, but not spinal cord or notochord markers. The main conclusion of this work is that IGF provides a positive signal initially uniformly expressed throughout the embryo that potentiates the effect of an organizer-specific negative signal mediated by Cerberus. The results are discussed in the context of the history of neural induction.</p>","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":" ","pages":"203897"},"PeriodicalIF":3.9,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138810532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation and oxidative stress impair preimplantation embryonic morphogenesis in allergic asthma model.","authors":"Che Ismail Wafriy, Y. S. Kamsani, M. Nor-Ashikin","doi":"10.2139/ssrn.4367239","DOIUrl":"https://doi.org/10.2139/ssrn.4367239","url":null,"abstract":"The incidence of allergic asthma has been increasing worldwide in recent decades. Also, an increasing number of women are suffering from poor pregnancy outcome. However, the causal relationship between allergic asthma and embryonic growth in terms of cell morphogenesis has not been well elucidated. Here, we investigated the impact of allergic asthma on the morphogenesis of preimplantation embryos. Twenty-four female BALB/c were randomly divided into control (PBS), 50-μg (OVA1), 100-μg (OVA2) and 150-μg (OVA3). On Days-0 and -14, mice were induced intraperitoneally (i.p) with ovalbumin (OVA). On Days-21 until -23, mice were challenged with OVA via intranasal instillation (i.n). Control animals were sensitized and challenged with PBS. At the end of treatment (Day-25), 2-cell embryos were retrieved and cultured in vitro until the blastocysts hatched. Results showed reduced number of preimplantation embryos at all developing stages in all treated groups (p ≤ 0.0001). Uneven blastomere size, partial compaction- and cavitation-activity, low formation of trophectoderm (TE), as well as cell fragmentation were noted in all the treated groups. Maternal serum interleukin (IL)-4, immunoglobulin (Ig)-E and 8-hydroxydeoxyguanosine (8-OHdG) were notably high (p ≤ 0.0001, p ≤ 0.01) in contrast with low total antioxidant capacity (TAOC) (p ≤ 0.0001). Our findings indicated that OVA-induced allergic asthma had compromised cell morphogenesis through reduced blastomere cleavage division, partial compaction and cavitation-activity, impairment of TE production, and cell fragmentation leading to embryonic cell death via OS mechanism.","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":"1943 1","pages":"203864"},"PeriodicalIF":3.9,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91204783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disrupted neurogenesis, gliogenesis, and ependymogenesis in the Ccdc85c knockout rat for hydrocephalus model.","authors":"Mehedi Hasan, Shizuka Konishi, Miyuu Tanaka, T. Izawa, J. Yamate, M. Kuwamura","doi":"10.2139/ssrn.4367238","DOIUrl":"https://doi.org/10.2139/ssrn.4367238","url":null,"abstract":"Coil-coiled domain containing 85c (Ccdc85c) is a causative gene for congenital hydrocephalus and subcortical heterotopia with frequent brain hemorrhage. We established Ccdc85c knockout (KO) rats and investigated the roles of CCDC85C and intermediate filament protein expression, including nestin, vimentin, GFAP, and cytokeratin AE1/AE3 during the lateral ventricle development in KO rats to evaluate the role of this gene. We found altered and ectopic expression of nestin and vimentin positive cells in the wall of the dorso-lateral ventricle in the KO rats during development from the age of postnatal day (P) 6, whereas both protein expression became faint in the wild-type rats. In the KO rats, there was a loss of cytokeratin expression on the surface of the dorso-lateral ventricle with ectopic expression and maldevelopment of ependymal cells. Our data also revealed disturbed GFAP expression at postnatal ages. These findings indicate that lack of CCDC85C disrupts the proper expression of intermediate filament proteins (nestin, vimentin, GFAP, and cytokeratin), and CCDC85C is necessary for normal neurogenesis, gliogenesis, and ependymogenesis.","PeriodicalId":29860,"journal":{"name":"Cells & Development","volume":"79 1","pages":"203858"},"PeriodicalIF":3.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79305322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}