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Modelling human brain development and disease with organoids 用类器官模拟人类大脑发育和疾病
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-12-12 DOI: 10.1038/s41580-024-00804-1
Marcella Birtele, Madeline Lancaster, Giorgia Quadrato
{"title":"Modelling human brain development and disease with organoids","authors":"Marcella Birtele, Madeline Lancaster, Giorgia Quadrato","doi":"10.1038/s41580-024-00804-1","DOIUrl":"10.1038/s41580-024-00804-1","url":null,"abstract":"Organoids are systems derived from pluripotent stem cells at the interface between traditional monolayer cultures and in vivo animal models. The structural and functional characteristics of organoids enable the modelling of early stages of brain development in a physiologically relevant 3D environment. Moreover, organoids constitute a tool with which to analyse how individual genetic variation contributes to the susceptibility and progression of neurodevelopmental disorders. This Roadmap article describes the features of brain organoids, focusing on the neocortex, and their advantages and limitations — in comparison with other model systems — for the study of brain development, evolution and disease. We highlight avenues for enhancing the physiological relevance of brain organoids by integrating bioengineering techniques and unbiased high-throughput analyses, and discuss future applications. As organoids advance in mimicking human brain functions, we address the ethical and societal implications of this technology. This Roadmap article discusses recent advances in the production and use of brain organoids to understand brain development and associated disorders. The path towards increasing organoid complexity and better maturation, to create more accurate and reproducible model systems, is outlined. Finally, the important ethical implications of these advances is discussed.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 5","pages":"389-412"},"PeriodicalIF":81.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815715","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
Calcium connects lysosomal damage to stress granule formation 钙将溶酶体损伤与应激颗粒形成联系起来
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-12-03 DOI: 10.1038/s41580-024-00817-w
Kim Baumann
{"title":"Calcium connects lysosomal damage to stress granule formation","authors":"Kim Baumann","doi":"10.1038/s41580-024-00817-w","DOIUrl":"10.1038/s41580-024-00817-w","url":null,"abstract":"A calcium-dependent pathway induces stress granule formation and promotes cell survival following lysosomal damage.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 1","pages":"10-10"},"PeriodicalIF":81.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760549","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
m6A ‘encodes’ a dedicated mRNA decay pathway m6A“编码”一个专用的mRNA衰变途径
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-12-03 DOI: 10.1038/s41580-024-00815-y
Eytan Zlotorynski
{"title":"m6A ‘encodes’ a dedicated mRNA decay pathway","authors":"Eytan Zlotorynski","doi":"10.1038/s41580-024-00815-y","DOIUrl":"10.1038/s41580-024-00815-y","url":null,"abstract":"Sites of N6-methyladenosine (m6A) in the coding region of mRNAs can induce a distinct, translation-dependent decay pathway involving mRNA translocation to P-bodies.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 1","pages":"8-8"},"PeriodicalIF":81.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760183","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
Origin, fate and function of extraembryonic tissues during mammalian development 哺乳动物发育过程中胚胎外组织的起源、命运和功能
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-12-03 DOI: 10.1038/s41580-024-00809-w
Shifaan Thowfeequ, Courtney W. Hanna, Shankar Srinivas
{"title":"Origin, fate and function of extraembryonic tissues during mammalian development","authors":"Shifaan Thowfeequ, Courtney W. Hanna, Shankar Srinivas","doi":"10.1038/s41580-024-00809-w","DOIUrl":"10.1038/s41580-024-00809-w","url":null,"abstract":"Extraembryonic tissues have pivotal roles in morphogenesis and patterning of the early mammalian embryo. Developmental programmes mediated through signalling pathways and gene regulatory networks determine the sequence in which fate determination and lineage commitment of extraembryonic tissues take place, and epigenetic processes allow the memory of cell identity and state to be sustained throughout and beyond embryo development, even extending across generations. In this Review, we discuss the molecular and cellular mechanisms necessary for the different extraembryonic tissues to develop and function, from their initial specification up until the end of gastrulation, when the body plan of the embryo and the anatomical organization of its supporting extraembryonic structures are established. We examine the interaction between extraembryonic and embryonic tissues during early patterning and morphogenesis, and outline how epigenetic memory supports extraembryonic tissue development. During mammalian embryogenesis, extraembryonic tissues are required for the patterning and morphogenesis of the embryo. This Review discusses how signalling networks and epigenetic modifications regulate the development and function of the different extraembryonic tissues during implantation, axis specification and gastrulation.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 4","pages":"255-275"},"PeriodicalIF":81.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763468","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
Fat cells have long-lasting (epigenetic) memory 脂肪细胞具有持久的（表观遗传）记忆
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-12-03 DOI: 10.1038/s41580-024-00816-x
Kim Baumann
{"title":"Fat cells have long-lasting (epigenetic) memory","authors":"Kim Baumann","doi":"10.1038/s41580-024-00816-x","DOIUrl":"10.1038/s41580-024-00816-x","url":null,"abstract":"Obesity-induced transcriptional and epigenetic alterations persist following weight loss, which negatively affects adipose tissue function and increases the propensity to regain weight.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 1","pages":"7-7"},"PeriodicalIF":81.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760039","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
Condensates trail the nucleus 凝析物跟随着原子核
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-12-03 DOI: 10.1038/s41580-024-00814-z
Lisa Heinke
{"title":"Condensates trail the nucleus","authors":"Lisa Heinke","doi":"10.1038/s41580-024-00814-z","DOIUrl":"10.1038/s41580-024-00814-z","url":null,"abstract":"Zhao et al. describe how nuclear deformation during confined cell migration affects chromatin organization and biomolecular condensates. Chromatin heterogeneity in the trailing nuclear half creates a permissive environment for condensate formation, with potential roles in nuclear mechanics and chromatin interactions.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 1","pages":"9-9"},"PeriodicalIF":81.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760701","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
Telomere function and regulation from mouse models to human ageing and disease 从小鼠模型到人类衰老和疾病的端粒功能和调控
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-11-29 DOI: 10.1038/s41580-024-00800-5
Corey Jones-Weinert, Laura Mainz, Jan Karlseder
{"title":"Telomere function and regulation from mouse models to human ageing and disease","authors":"Corey Jones-Weinert, Laura Mainz, Jan Karlseder","doi":"10.1038/s41580-024-00800-5","DOIUrl":"10.1038/s41580-024-00800-5","url":null,"abstract":"Telomeres protect the ends of chromosomes but shorten following cell division in the absence of telomerase activity. When telomeres become critically short or damaged, a DNA damage response is activated. Telomeres then become dysfunctional and trigger cellular senescence or death. Telomere shortening occurs with ageing and may contribute to associated maladies such as infertility, neurodegeneration, cancer, lung dysfunction and haematopoiesis disorders. Telomere dysfunction (sometimes without shortening) is associated with various diseases, known as telomere biology disorders (also known as telomeropathies). Telomere biology disorders include dyskeratosis congenita, Høyeraal–Hreidarsson syndrome, Coats plus syndrome and Revesz syndrome. Although mouse models have been invaluable in advancing telomere research, full recapitulation of human telomere-related diseases in mice has been challenging, owing to key differences between the species. In this Review, we discuss telomere protection, maintenance and damage. We highlight the differences between human and mouse telomere biology that may contribute to discrepancies between human diseases and mouse models. Finally, we discuss recent efforts to generate new ‘humanized’ mouse models to better model human telomere biology. A better understanding of the limitations of mouse telomere models will pave the road for more human-like models and further our understanding of telomere biology disorders, which will contribute towards the development of new therapies. Telomere dysfunction, usually owing to shortening, activates cellular senescence and can contribute to age-associated diseases and cancer. Mouse models are crucial for telomere research, but human and mouse telomeres have key differences. This Review discusses telomere maintenance and damage, and recent efforts to generate ‘humanized’-telomere mouse models.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 4","pages":"297-313"},"PeriodicalIF":81.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142753112","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
Three decades of protein-fragment complementation 蛋白质片段互补三十年
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-11-28 DOI: 10.1038/s41580-024-00813-0
Stephen W. Michnick
{"title":"Three decades of protein-fragment complementation","authors":"Stephen W. Michnick","doi":"10.1038/s41580-024-00813-0","DOIUrl":"10.1038/s41580-024-00813-0","url":null,"abstract":"This year marks the 30th anniversary of the publication of a novel approach to measuring protein–protein interactions (PPIs) in living cells, called the ubiquitin-based split-protein sensor (USPS), the inspiration for the protein-fragment complementation assays (PCAs) that followed. Here I provide a brief history of PCAs and discuss advances in their applications and possible future developments. Stephen Michnick provides a brief history of protein-fragment complementation — an approach to studying protein–protein interactions in living cells — and discusses advances in its applications and possible future developments.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 1","pages":"3-4"},"PeriodicalIF":81.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735808","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
How proteins sense their cellular environment 蛋白质如何感知细胞环境
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-11-28 DOI: 10.1038/s41580-024-00812-1
Monika Fuxreiter
{"title":"How proteins sense their cellular environment","authors":"Monika Fuxreiter","doi":"10.1038/s41580-024-00812-1","DOIUrl":"10.1038/s41580-024-00812-1","url":null,"abstract":"The cellular environment is critical to protein function. How is information from many cellular components decoded in order to fine-tune biological activity? New models of biomolecular recognition raise the possibility that proteins engage in specific, yet fuzzy, interactions with their functional partners, which can provide a readout mechanism of the cellular context. Manipulating the cellular context to control protein function offers new therapeutic opportunities. In this Comment article, Monika Fuxreiter discusses possible roles of dynamic, fuzzy protein interactions and their importance in changing cellular environments.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 3","pages":"169-170"},"PeriodicalIF":81.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735584","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
Exploiting cell cycle-dependent dephosphorylation for mitosis-specific protein recruitment 利用细胞周期依赖性去磷酸化实现有丝分裂特异性蛋白质招募
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-11-20 DOI: 10.1038/s41580-024-00808-x
Xiaofu Cao
{"title":"Exploiting cell cycle-dependent dephosphorylation for mitosis-specific protein recruitment","authors":"Xiaofu Cao","doi":"10.1038/s41580-024-00808-x","DOIUrl":"10.1038/s41580-024-00808-x","url":null,"abstract":"In this Tools of the Trade article, Cao (Baskin lab) discusses the development of MARS, which enables mitosis-specific recruitment of enzymes to the plasma membrane, exploiting the cell cycle’s natural regulation of PLEKHA5 phosphorylation.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"26 1","pages":"5-5"},"PeriodicalIF":81.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678628","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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