{"title":"Recent insights into the in vitro culture systems for mammalian embryos","authors":"Zhiyuan Guo , Wentao Zhao , Hongmei Wang , Jinglei Zhai","doi":"10.1016/j.gde.2025.102309","DOIUrl":"10.1016/j.gde.2025.102309","url":null,"abstract":"<div><div>Mammalian early embryonic development is the cornerstone for a healthy life. Any aberrations during early embryonic development may lead to adverse pregnancy outcomes. Therefore, the comprehensive study of embryonic developmental events is essential for understanding biological and pathological pregnancy. However, due to mammalian embryo development taking place in the uterus, it is hard to directly observe the developing embryos that are undergoing dramatic and complex morphologies, proliferation, and differentiation. The <em>in vitro</em> culture (IVC) of mammalian embryos is a pivotal model for studying developmental events. Recent advancements in establishing long-term culture systems for early mammalian embryos have allowed researchers to culture human embryos up to the embryonic day (E) 14 ethical limitations and extend mouse and macaque embryos to early organogenesis. Here, we review the development of IVC systems for mammalian embryos, emphasize the important improvements in culture elements, and offer our perspectives on potential future optimizations of IVC systems.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"91 ","pages":"Article 102309"},"PeriodicalIF":3.7,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015665","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":"Genome folding by cohesin","authors":"Shutao Qi , Zhubing Shi , Hongtao Yu","doi":"10.1016/j.gde.2025.102310","DOIUrl":"10.1016/j.gde.2025.102310","url":null,"abstract":"<div><div>Chromosomes in eukaryotic cells undergo compaction at multiple levels and are folded into hierarchical structures to fit into the nucleus with limited dimensions. Three-dimensional genome organization needs to be coordinated with chromosome-templated processes, including DNA replication and gene transcription. As an ATPase molecular machine, the cohesin complex is a major driver of genome folding, which regulates transcription by modulating promoter–enhancer contacts. Here, we review our current understanding of genome folding by cohesin. We summarize the available evidence supporting a role of loop extrusion by cohesin in forming chromatin loops and topologically associating domains. We describe different conformations of cohesin and discuss the regulation of loop extrusion by cohesin-binding factors and loop-extrusion barriers. Finally, we propose a dimeric inchworm model for cohesin-mediated loop extrusion.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"91 ","pages":"Article 102310"},"PeriodicalIF":3.7,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015663","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}
Xin Yu , Qianqian Li , Xuan Shao , Amanda N Sferruzzi-Perri , Yan-Ling Wang
{"title":"Fine-tuned programming of placenta trophoblast determines optimal maternal–fetal nutrient allocation","authors":"Xin Yu , Qianqian Li , Xuan Shao , Amanda N Sferruzzi-Perri , Yan-Ling Wang","doi":"10.1016/j.gde.2024.102305","DOIUrl":"10.1016/j.gde.2024.102305","url":null,"abstract":"<div><div>Maternal health and fetal survival during pregnancy encapsulate a paradox of cooperation and competition. One particularly intriguing aspect of this paradox involves the optimal allocation of nutrients between the mother and fetus. Despite this, the precise mechanisms governing nutrient allocation remain elusive. This review aims to provide a summation of latest research that is improving our understanding of placental metabolism and nutrient allocation between the mother and the fetus. It highlights that in addition to transporter-mediated processes for glucose, fatty acid, and amino acid transport, the human placental trophoblast utilizes a unique macropinocytosis strategy to uptake large molecules from maternal circulation in conditions of nutrient stress. In addition, placental trophoblasts undergo intensive metabolic programming and post-translational modifications during the differentiation process, which regulate trophoblast cell fate, function, and pregnancy outcomes. A number of imprinted genes have been identified to play crucial roles in balancing allocation between the mother and the fetus, yet their role in trophoblast macropinocytosis and metabolic reprogramming requires study. Further work in this area of placental nutrient allocation is essential for identifying the pathogenesis of pregnancy disorders and developing novel therapeutic interventions.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"91 ","pages":"Article 102305"},"PeriodicalIF":3.7,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015662","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":"Beyond equilibrium: roles of RNAs in condensate control","authors":"Fernando Muzzopappa, Fabian Erdel","doi":"10.1016/j.gde.2024.102304","DOIUrl":"10.1016/j.gde.2024.102304","url":null,"abstract":"<div><div>Membraneless subcompartments organize various activities in the cell nucleus. Some of them are formed through phase separation that is driven by the polymeric and multivalent nature of biomolecules. Here, we discuss the role of RNAs in regulating nuclear subcompartments. On the one hand, chromatin-associated RNA molecules may act as binding platforms that recruit molecules to specific genomic loci. On the other hand, RNA molecules may act as multivalent scaffolds that stabilize biomolecular condensates. The active production and processing of RNAs inside of nuclear subcompartments drives them out of thermodynamic equilibrium and thereby modulates their properties. Accordingly, RNA content and transcriptional activity appear as key determinants of the biophysical and functional nature of nuclear substructures.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"91 ","pages":"Article 102304"},"PeriodicalIF":3.7,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015661","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}
Manuel Ferrando-Bernal , Colin M Brand , John A Capra
{"title":"Inferring human phenotypes using ancient DNA: from molecules to populations","authors":"Manuel Ferrando-Bernal , Colin M Brand , John A Capra","doi":"10.1016/j.gde.2024.102283","DOIUrl":"10.1016/j.gde.2024.102283","url":null,"abstract":"<div><div>The increasing availability of ancient DNA (aDNA) from human groups across space and time has yielded deep insights into the movements of our species. However, given the challenges of mapping from genotype to phenotype, aDNA has revealed less about the phenotypes of ancient individuals. In this review, we highlight recent advances in inferring ancient phenotypes — from the molecular to population scale — with a focus on applications enabled by new machine learning approaches. The genetic architecture of complex traits across human groups suggests that the prediction of individual-level complex traits, like behavior or disease risk, is often challenging across the relevant evolutionary distances. Thus, we propose an approach that integrates predictions of molecular phenotypes, whose mechanisms are more conserved, with nongenetic data.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"90 ","pages":"Article 102283"},"PeriodicalIF":3.7,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747917","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":"In vitro dynamics of DNA loop extrusion by structural maintenance of chromosomes complexes","authors":"Marius Rutkauskas, Eugene Kim","doi":"10.1016/j.gde.2024.102284","DOIUrl":"10.1016/j.gde.2024.102284","url":null,"abstract":"<div><div>Genomic DNA inside the cell’s nucleus is highly organized and tightly controlled by the structural maintenance of chromosomes (SMC) protein complexes. These complexes fold genomes by creating and processively enlarging loops, a process called loop extrusion. After more than a decade of accumulating indirect evidence, recent <em>in vitro</em> single-molecule studies confirmed loop extrusion as an evolutionarily conserved function among eukaryotic and prokaryotic SMCs. These studies further provided important insights into mechanisms and regulations of these universal molecular machines, which will be discussed in this minireview.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"90 ","pages":"Article 102284"},"PeriodicalIF":3.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699491","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":"Novelty versus innovation of gene regulatory elements in human evolution and disease","authors":"Anushka Katikaneni , Craig B Lowe","doi":"10.1016/j.gde.2024.102279","DOIUrl":"10.1016/j.gde.2024.102279","url":null,"abstract":"<div><div>It is not currently understood how much of human evolution is due to modifying existing functional elements in the genome versus forging novel elements from nonfunctional DNA. Many early experiments that aimed to assign genetic changes on the human lineage to their resulting phenotypic change have focused on mutations that modify existing elements. However, a number of recent studies have highlighted the potential ease and importance of forging novel gene regulatory elements from nonfunctional sequences on the human lineage. In this review, we distinguish gene regulatory element novelty from innovation. We propose definitions for these terms and emphasize their importance in studying the genetic basis of human uniqueness. We discuss why the forging of novel regulatory elements may have been less emphasized during the previous decades, and why novel regulatory elements are likely to play a significant role in both human adaptation and disease.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"90 ","pages":"Article 102279"},"PeriodicalIF":3.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699598","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":"Circuit integration by transplanted human neurons","authors":"Qiang Yuan , Su-Chun Zhang","doi":"10.1016/j.gde.2024.102225","DOIUrl":"10.1016/j.gde.2024.102225","url":null,"abstract":"<div><div>Transplantation-based cell therapy holds the potential to offer sustained and physiological repair for neurological diseases and injuries, which requires the integration of transplanted neurons into the neural circuits of the human brain. Recent studies involving transplantation of human pluripotent stem cell–derived neural progenitors into the brain of model animals reveal the remarkable capacity of grafted immature human neurons to mature, project axons in a long distance, and form both pre- and postsynaptic connections with host neurons, corresponding to functional recovery. Strikingly, this circuit integration depends largely on the identity of the transplanted cells and may be modified by external stimuli. This realization begs for enriched authentic target cells for transplantation and combination with rehabilitation for better therapeutic outcomes.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102225"},"PeriodicalIF":3.7,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699886","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":"Unveiling the potential: implications of successful somatic cell-to-ganglion organoid reprogramming","authors":"Dongchang Xiao , Shuting Liu , Mengqing Xiang","doi":"10.1016/j.gde.2024.102227","DOIUrl":"10.1016/j.gde.2024.102227","url":null,"abstract":"<div><div>Organoids have a wide range of potential applications in areas such as organ development, precision medicine, regenerative medicine, drug screening, disease modeling, and gene editing. Currently, most organoids are generated through three-dimensional (3D) <em>in vitro</em> culture of adult stem cells or pluripotent stem cells. However, this method of generating organoids still has several limitations and challenges, including complex manipulations, costly culturing materials, extended time requirements, and certain heterogeneity. Recently, we have found that fibroblasts, when overexpressing several key regulatory transcription factors, are able to directly and rapidly generate two types of ganglion organoids: sensory ganglion (SG) and autonomic ganglion (AG) organoids. They have structures and electrophysiological properties similar to those of endogenous organs in the body. Here, we provide a brief overview of organoid development, focusing on direct reprogramming of SG and AG organoids and their transplantation and regeneration. Finally, the advantages and prospects of direct reprogramming of organoids are discussed.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"89 ","pages":"Article 102227"},"PeriodicalIF":3.7,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699889","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}