{"title":"The pluripotency state of human embryonic stem cells derived from single blastomeres of eight-cell embryos","authors":"","doi":"10.1016/j.cdev.2024.203935","DOIUrl":"10.1016/j.cdev.2024.203935","url":null,"abstract":"<div><p>Human embryonic stem cells (hESCs) derived from blastocyst stage embryos present a primed state of pluripotency, whereas mouse ESCs (mESCs) display naïve pluripotency. Their unique characteristics make naïve hESCs more suitable for particular applications in biomedical research. This work aimed to derive hESCs from single blastomeres and determine their pluripotency state, which is currently unclear. We derived hESC lines from single blastomeres of 8-cell embryos and from whole blastocysts, and analysed several naïve pluripotency indicators, their transcriptomic profile and their trilineage differentiation potential. No significant differences were observed between blastomere-derived hESCs (bm-hESCs) and blastocyst-derived hESCs (bc-hESCs) for most naïve pluripotency indicators, including TFE3 localization, mitochondrial activity, and global DNA methylation and hydroxymethylation, nor for their trilineage differentiation potential. Nevertheless, bm-hESCs showed an increased single-cell clonogenicity and a higher expression of naïve pluripotency markers at early passages than bc-hESCs. Furthermore, RNA-seq revealed that bc-hESCs overexpressed a set of genes related to the post-implantational epiblast. Altogether, these results suggest that bm-hESCs, although displaying primed pluripotency, would be slightly closer to the naïve end of the pluripotency continuum than bc-hESCs.</p></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"179 ","pages":"Article 203935"},"PeriodicalIF":3.9,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667290124000366/pdfft?md5=b40ca074f6560789f44ccd6742c38a54&pid=1-s2.0-S2667290124000366-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Oct4-related PouV gene, pou5f3, mediates isthmus development in zebrafish by directly and dynamically regulating pax2a","authors":"","doi":"10.1016/j.cdev.2024.203933","DOIUrl":"10.1016/j.cdev.2024.203933","url":null,"abstract":"<div><p>Using a transgenic zebrafish line harboring a heat-inducible dominant-interference <em>pou5f3</em> gene (<em>en-pou5f3</em>), we reported that this <em>PouV</em> gene is involved in isthmus development at the midbrain-hindbrain boundary (MHB), which patterns the midbrain and cerebellum. Importantly, the functions of <em>pou5f3</em> reportedly differ before and after the end of gastrulation. In the present study, we examined in detail the effects of <em>en-pou5f3</em> induction on isthmus development during embryogenesis. When <em>en-pou5f3</em> was induced around the end of gastrulation (bud stage), the isthmus was abrogated or deformed by the end of somitogenesis (24 hours post-fertilization). At this stage, the expression of MHB markers –– such as <em>pax2a</em>, <em>fgf8a</em>, <em>wnt1</em>, and <em>gbx2</em> –– was absent in embryos lacking the isthmus structure, whereas it was present, although severely distorted, in embryos with a deformed isthmus. We further found that, after <em>en-pou5f3</em> induction at late gastrulation, <em>pax2a</em>, <em>fgf8a</em>, and <em>wnt1</em> were immediately and irreversibly downregulated, whereas the expression of <em>en2a</em> and <em>gbx2</em> was reduced only weakly and slowly. Induction of <em>en-pou5f3</em> at early somite stages also immediately downregulated MHB genes, particularly <em>pax2a</em>, but their expression was restored later. Overall, the data suggested that <em>pou5f3</em> directly upregulates at least <em>pax2a</em> and possibly <em>fgf8a</em> and <em>wnt1</em>, which function in parallel in establishing the MHB, and that the role of <em>pou5f3</em> dynamically changes around the end of gastrulation. We next examined the transcriptional regulation of <em>pax2a</em> using both <em>in vitro</em> and <em>in vivo</em> reporter analyses; the results showed that two upstream 1.0-kb regions with sequences conserved among vertebrates specifically drove transcription at the MHB. These reporter analyses confirmed that development of the isthmic organizer is regulated by <em>PouV</em> through direct regulation of <em>pax2/pax2a</em> in vertebrate embryos.</p></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"179 ","pages":"Article 203933"},"PeriodicalIF":3.9,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667290124000342/pdfft?md5=b61986f43b731fec0690814d585adbf7&pid=1-s2.0-S2667290124000342-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Trusting the forces of our cell lines","authors":"","doi":"10.1016/j.cdev.2024.203931","DOIUrl":"10.1016/j.cdev.2024.203931","url":null,"abstract":"<div><p>Cells isolated from their native tissues and cultured <em>in vitro</em> face different selection pressures than those cultured <em>in vivo</em>. These pressures induce a profound transformation that reshapes the cell, alters its genome, and transforms the way it senses and generates forces. In this perspective, we focus on the evidence that cells cultured on conventional polystyrene substrates display a fundamentally different mechanobiology than their <em>in vivo</em> counterparts. We explore the role of adhesion reinforcement in this transformation and to what extent it is reversible. We argue that this mechanoadaptation is often understood as a mechanical memory. We propose some strategies to mitigate the effects of on-plastic culture on mechanobiology, such as organoid-inspired protocols or mechanical priming. While isolating cells from their native tissues and culturing them on artificial substrates has revolutionized biomedical research, it has also transformed cellular forces. Only by understanding and controlling them, we can improve their truthfulness and validity.</p></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"179 ","pages":"Article 203931"},"PeriodicalIF":3.9,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667290124000329/pdfft?md5=41d84aa12a8038508a4830be7313c50d&pid=1-s2.0-S2667290124000329-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A double-negative feedback loop mediated by non-coding RNAs contributes to tooth morphogenesis","authors":"","doi":"10.1016/j.cdev.2024.203932","DOIUrl":"10.1016/j.cdev.2024.203932","url":null,"abstract":"<div><p>Tooth morphogenesis is a critically ordered process manipulated by a range of signaling factors. Particularly, the involvement of fine-tuned signaling mediated by non-coding RNAs has been of longstanding interest. Here, we revealed a double-negative feedback loop acted by a long non-coding RNA (LOC102159588) and a microRNA (miR-133b) that modulated tooth morphogenesis of miniature swine. Mechanistically, miR-133b repressed the transcription of LOC102159588 through downstream target Sp1. Conversely, LOC102159588 not only inhibited the transport of pre-miR-133b from the nucleus to the cytoplasm by regulating exportin-5 but also served as a sponge in the cytoplasm, suppressing functional miR-133b. Together, the double-negative feedback loop maintained normal tooth morphogenesis by modulating endogenous apoptosis. Related disruptions would lead to an arrest of tooth development and may result in tooth malformations.</p></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"179 ","pages":"Article 203932"},"PeriodicalIF":3.9,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667290124000330/pdfft?md5=8c8a02cc6015c78194e1ee8f787ee9a6&pid=1-s2.0-S2667290124000330-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The significance of Ethel Browne's research on Hydra for the organizer concept","authors":"","doi":"10.1016/j.cdev.2024.203907","DOIUrl":"10.1016/j.cdev.2024.203907","url":null,"abstract":"<div><p><span>This article focuses on the roots of the organizer concept, which was developed by Hans Spemann during his studies of early embryonic development in amphibians. The fundamental properties of this axis-inducing signaling center have been elucidated through pioneering molecular research by Eddy De Robertis' laboratory and other researchers. Evolutionary comparisons have disclosed the presence of this signaling center, involving the interaction of Wnt and TGF-beta signaling pathways, existed not only in vertebrates but also in basal Metazoa such as Cnidaria. – Notably, even prior to the groundbreaking experiments conducted by Hilde Mangold and Hans Spemann, Ethel Browne conducted similar transplantation experiments on </span><em>Hydra</em><span> polyps. They were performed under the guidance of Thomas H Morgan and in the laboratory of Edmund B Wilson. Howard Lenhoff was the first to draw connections between Ethel Browne's transplantation experiments and those of Spemann and Mangold, igniting a vivid debate on the precedence of the organizer concept and its recognition in Nobel Prize considerations. This review critically compares the experiments conducted by Spemann and Mangold with those preceding their seminal work, concluding that the organizer concept clearly builds upon earlier research aimed at understanding developmental gradients, such as in the simple model </span><em>Hydra</em>. However, these approaches were not pursued further by Morgan, who shifted his focus towards unraveling the genetic control of development in flies, an approach that ultimately revealed the molecular identity of the Spemann organizer in vertebrates.</p></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"178 ","pages":"Article 203907"},"PeriodicalIF":3.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139991300","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":"Never-ending story of Brachyury: From short-tailed mice to tailless primates","authors":"","doi":"10.1016/j.cdev.2023.203896","DOIUrl":"10.1016/j.cdev.2023.203896","url":null,"abstract":"<div><p>The history of developmental biology starts from the almost simultaneous discoveries of the Organizer of axial structures in amphibians by Spemann and Mangold in Freiburg and of the Brachyury mutant in mammals by the Dobrovolskaya-Zavadskaya laboratory at the Curie Institute and its follow-up studies in the Leslie Dunn laboratory at Columbia University. Following the Organizer's discovery, the inductive activity of several other embryonic tissues was found, including that of the ear primordium by Boris Balinsky in Kiev. Initially, the experimental embryological and genetic lines of research existed independently of each other, but after they met at the bench of Salome Gluecksohn, they strengthened and cross-fertilized each other, eventually leading to developmental genetics, which later became known as developmental biology. It appears that the regulatory activities of Brachyury and related T-box proteins in general are at the heart of the development of all vertebrates. These activities are fundamental and have been discovered in several model organisms subjected to mutagenesis, exemplified by the story of George Streisinger's discovery of the <em>no tail</em> mutant in zebrafish. This essay describes the history of Brachyury studies, their connection to an idea of embryonic induction by Organizer, and an impact of Brachyury and related genes on various fields of research from embryology and cell biology to medical genetics and evolutionary theory.</p></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"178 ","pages":"Article 203896"},"PeriodicalIF":3.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667290123000724/pdfft?md5=c0e9d0cc5d7d0ab3680c47888fcbe3d1&pid=1-s2.0-S2667290123000724-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138627692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Spemann-Mangold organizer discovery and society","authors":"","doi":"10.1016/j.cdev.2024.203906","DOIUrl":"10.1016/j.cdev.2024.203906","url":null,"abstract":"<div><p>This paper analyzes the influence of Hans Spemann and Hilde Mangold's discovery of the embryonic organizer on society outside the narrower confines of embryology. It begins by overviewing how in the 1920s–1930s, the organizer discovery fit well into the agenda of both right-wing and left-wing political camps, as it supported holistic theories of biological development that aligned with their ideological views. The paper then explores the organizer's influence on the formation and interdisciplinary discussions of the 1930s Cambridge Theoretical Biology Club. Club member C.H. Waddington's concept of the epigenetic landscape, inspired in part by Spemann and Mangold's work, went on to impact diverse fields including mathematics, psychology, anthropology, architecture, and art. Examples include mathematician René Thom's catastrophe landscapes and the field of ekistics (the science of human settlements). Spemann and Mangold's creation of an embryo chimera by combining tissues from different newt species also helped shape philosophers' and artists' understanding of the relationship between nature and technology as an integrated whole rather than separate entities. Additionally, Spemann's embryonic field concept helped influence field theories in other areas of science, and thinkers have pointed out metaphorical similarities between the organizer experiment and philosophical dialectics, film editing, or historical events. However, several factors likely limited the long-term societal impact of Spemann's holistic perspective, notably the rise of molecular biology and DNA-centric reductionist views of biology in the mid-late 20th century. While such reductionism still dominates public perceptions of biology, there seems to be a renewed openness to holistic perspectives reminiscent of Spemann's views.</p></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"178 ","pages":"Article 203906"},"PeriodicalIF":3.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266729012400007X/pdfft?md5=041baec31ebd47b7a2938c41d23e9bea&pid=1-s2.0-S266729012400007X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139966067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hilde Mangold: Original microscope slides and records of the gastrula organizer experiments","authors":"","doi":"10.1016/j.cdev.2024.203909","DOIUrl":"10.1016/j.cdev.2024.203909","url":null,"abstract":"<div><p>The discovery of the amphibian gastrula organizer and its publication by Hans Spemann and Hilde Mangold in 1924 is a foundation of experimental embryology, and has shaped our understanding of embryonic induction and pattern formation in vertebrates until today. The original publication is a piece of scientific art, characterized by the meticulous hand drawings by Hilde Mangold, as well as the text that develops mechanistic concepts of modern embryology. While historic microphotographs of specimens got lost, the original microscope slides and Hilde Mangold's laboratory notebook have been secured in embryological collections until today. Here, we make the original data of the six embryonic specimens reported in 1924, as well as the laboratory notebook, available in an accessible digital format. Together, these data shed light on the scientific process that led to the discovery, and should help to make the experiments on the most important signalling center in early vertebrate development transparent for generations of embryologists to come.</p></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"178 ","pages":"Article 203909"},"PeriodicalIF":3.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266729012400010X/pdfft?md5=771a9b7e2f733db1ce54953764d6ae46&pid=1-s2.0-S266729012400010X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Roberto Mayor (Editor in Chief of CELLS & DEVELOPMENT)
{"title":"Reprint of: Moving forward","authors":"Roberto Mayor (Editor in Chief of CELLS & DEVELOPMENT)","doi":"10.1016/j.cdev.2024.203937","DOIUrl":"10.1016/j.cdev.2024.203937","url":null,"abstract":"","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"178 ","pages":"Article 203937"},"PeriodicalIF":3.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767584","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}