The mouse alpha-globin cluster: a paradigm for studying genome regulation and organization.
Abstract The mammalian globin gene clusters provide a paradigm for studying the relationship between genome structure and function. As blood stem cells undergo lineage specification and differentiation to form red blood cells, the chromatin structure and expression of the α-globin cluster change. The gradual activation of the α-globin genes in well-defined cell populations has enabled investigation of the structural and functional roles of its enhancers, promoters and boundary elements. Recent studies of gene regulatory processes involving these elements at the mouse α-globin cluster have brought...
Source: Current Opinion in Genetics and Development - November 19, 2020 Category: Genetics & Stem Cells Authors: Oudelaar AM, Beagrie RA, Kassouf MT, Higgs DR Tags: Curr Opin Genet Dev Source Type: research

Novel orthogonal methods to uncover the complexity and diversity of nuclear architecture.
Abstract Recent years have seen a vast expansion of knowledge on three-dimensional (3D) genome organization. The majority of studies on chromosome topology consists of pairwise interaction data of bulk populations of cells and therefore conceals heterogenic and more complex folding patterns. Here, we discuss novel methodologies to study the variation in genome topologies between different cells and techniques that allow analysis of complex, multi-way interactions. These technologies will aid the interpretation of genome-wide chromosome conformation data and provide strategies to further dissect the interplay betwe...
Source: Current Opinion in Genetics and Development - November 18, 2020 Category: Genetics & Stem Cells Authors: Tjalsma SJ, de Laat W Tags: Curr Opin Genet Dev Source Type: research

Enhancer-promoter communication: hubs or loops?
Abstract There has been a sea change in our view of transcription regulation during the past decade (Fukaya et al., 2016, Lim et al., 2018, Hnisz et al., 2017 [3], Liu et al., 2018 [4], Kato et al., 2012). Classical models of enhancer-promoter interactions and the stepwise assembly of individual RNA Polymerase II (Pol II) complexes have given way to the realization that active transcription foci contain clusters-hubs-of transcriptional activators and Pol II. Here we summarize recent findings pointing to the occurrence of transcription hubs and the implications of such hubs on the regulation of gene activity. ...
Source: Current Opinion in Genetics and Development - November 14, 2020 Category: Genetics & Stem Cells Authors: Lim B, Levine MS Tags: Curr Opin Genet Dev Source Type: research

Editorial overview: Neurodevelopment Diseases and Neurogenetics pivot towards mechanisms and therapies.
PMID: 33176916 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development)
Source: Current Opinion in Genetics and Development - November 8, 2020 Category: Genetics & Stem Cells Authors: Geschwind DH, Gleeson JG Tags: Curr Opin Genet Dev Source Type: research

Editorial overview: Cell reprogramming, regeneration and repair.
PMID: 33143849 [PubMed - in process] (Source: Current Opinion in Genetics and Development)
Source: Current Opinion in Genetics and Development - October 1, 2020 Category: Genetics & Stem Cells Authors: Jacinto A, Liu P Tags: Curr Opin Genet Dev Source Type: research

New gene discoveries highlight functional convergence in autism and related neurodevelopmental disorders.
Abstract Over the last two years, remarkable gene discovery efforts have implicated disruption of pathways involving gene regulatory functions and neuronal processes in autism spectrum disorder (ASD), and more broadly defined neurodevelopmental disorders (NDDs). Functional studies in the developing brain and across cell types demonstrate that the spatiotemporal expression patterns of many of these genes coalesce on subnetworks with distinct developmental trajectories. Here, we review the convergent biological processes derived from gene discovery and functional genomics in ASD and NDD from 2018-2020. We further pr...
Source: Current Opinion in Genetics and Development - August 22, 2020 Category: Genetics & Stem Cells Authors: Moyses-Oliveira M, Yadav R, Erdin S, Talkowski ME Tags: Curr Opin Genet Dev Source Type: research

Microglial ontogeny, diversity and neurodevelopmental functions.
Abstract Microglia are instrumental to the development, function, homeostasis and pathologies of the central nervous system. These brain-resident macrophages arise early in embryogenesis and seed the developing brain, where they differentiate in response to cues provided by their neural niche. Throughout life, microglia regulate the neural tissue through a variety of cellular functions influenced by intrinsic and extrinsic factors. Despite their importance, we are only starting to uncover how microglia colonize the brain, adopt distinct functional states during development and the long-term impact of early alterat...
Source: Current Opinion in Genetics and Development - August 16, 2020 Category: Genetics & Stem Cells Authors: Thion MS, Garel S Tags: Curr Opin Genet Dev Source Type: research

Vertebrate brain regeneration - a community effort of fate-restricted precursor cell types.
Abstract The process of regeneration describes the full restoration of tissue after destruction from injury or disease. Most mammals show very limited ability for regeneration of adult organs, while vertebrate models of regeneration such as fish and salamanders, allow to study regeneration mechanism of the brain, heart, limbs, retina, and other organs in adults. The regenerative abilities of teleost fish are well documented, but the cellular sources for regeneration, the specificity of source cells for restored cell types, as well as the extent and fidelity of cell replacement are only beginning to be revealed for...
Source: Current Opinion in Genetics and Development - August 6, 2020 Category: Genetics & Stem Cells Authors: Lange C, Brand M Tags: Curr Opin Genet Dev Source Type: research

Human adaptation over the past 40,000 years.
Abstract Over the past few years several methodological and data-driven advances have greatly improved our ability to robustly detect genomic signatures of selection in humans. New methods applied to large samples of present-day genomes provide increased power, while ancient DNA allows precise estimation of timing and tempo. However, despite these advances, we are still limited in our ability to translate these signatures into understanding about which traits were actually under selection, and why. Combining information from different populations and timescales may allow interpretation of selective sweeps. Other m...
Source: Current Opinion in Genetics and Development - July 30, 2020 Category: Genetics & Stem Cells Authors: Mathieson I Tags: Curr Opin Genet Dev Source Type: research

Disentangling the paradox of the PCDH19 clustering epilepsy, a disorder of cellular mosaics.
Abstract PCDH19 Clustering Epilepsy (CE) is an intriguing early-onset seizure, autism and neurocognitive disorder with unique inheritance. The causative gene, PCDH19, is on the X-chromosome and encodes a cell-cell adhesion protein with restricted expression during brain development. Unlike other X-linked disorders, PCDH19-CE manifests in heterozygous females. Strikingly, hemizygous males are not affected. However, males with postzygotic somatic mutation in PCDH19 are affected and clinically similar to the affected females. PCDH19-CE is a disorder of cellular mosaicism. The coexistence of two different, but otherwi...
Source: Current Opinion in Genetics and Development - July 25, 2020 Category: Genetics & Stem Cells Authors: Gecz J, Thomas PQ Tags: Curr Opin Genet Dev Source Type: research

Regeneration of the pancreas: proliferation and cellular conversion of surviving cells.
Abstract The most common pancreas-related disorders are diabetes, pancreatitis and different types of pancreatic cancers. Diabetes is a chronic condition which results from insufficient functional β-cell mass, either as a result of an autoimmune destruction of insulin producing β-cells, or as their death or de-differentiation following years of hyperactivity to compensate for insulin resistance. Chronic pancreatitis leads to cell death and can develop into diabetes or pancreatic cancer. To stimulate regeneration in such pathologies, it is of high importance to evaluate the endogenous regeneration capacit...
Source: Current Opinion in Genetics and Development - July 24, 2020 Category: Genetics & Stem Cells Authors: Sever D, Grapin-Botton A Tags: Curr Opin Genet Dev Source Type: research

Rising from the ashes: cellular senescence in regeneration.
Abstract Cellular senescence has recently become causally implicated in pathological ageing. Hence, a great deal of research is currently dedicated towards developing senolytic agents to selectively kill senescent cells. However, senescence also plays important roles in a range of physiological processes including during organismal development, providing a barrier to tumorigenesis and in limiting fibrosis. Recent evidence also suggests a role for senescence in coordinating tissue remodelling and in the regeneration of complex structures. Through its non-cell-autonomous effects, a transient induction of senescence ...
Source: Current Opinion in Genetics and Development - July 24, 2020 Category: Genetics & Stem Cells Authors: Walters HE, Yun MH Tags: Curr Opin Genet Dev Source Type: research

Generations of genomes: advances in paleogenomics technology and engagement for Indigenous people of the Americas.
Abstract For decades, scientists have collected genomic information from Indigenous peoples and their ancestors with the goal of elucidating human migration events, understanding ancestral origins, and identifying ancestral variants contributing to disease. However, such studies may not have offered much benefit to the Indigenous groups who contributed DNA, and many have instead perpetuated stereotypes and other harms. With recent advances in genomic technology facilitating the study of both ancient and present-day DNA, researchers and Indigenous communities have new opportunities to begin collaboratively addressi...
Source: Current Opinion in Genetics and Development - July 24, 2020 Category: Genetics & Stem Cells Authors: Tsosie KS, Begay RL, Fox K, Garrison NA Tags: Curr Opin Genet Dev Source Type: research

Methods for detecting introgressed archaic sequences.
Abstract Analysis of genome sequences from archaic and modern humans have revealed multiple episodes of admixture between highly-diverged population groups. Statistical methods that attempt to localize DNA segments introduced by these events offer a powerful tool to investigate recent human evolution. We review recent advances in methods for detecting introgressed sequences. PMID: 32717667 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development)
Source: Current Opinion in Genetics and Development - July 23, 2020 Category: Genetics & Stem Cells Authors: Sankararaman S Tags: Curr Opin Genet Dev Source Type: research

Editorial overview: Taking measure of developing plants and animals.
PMID: 32718808 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development)
Source: Current Opinion in Genetics and Development - July 23, 2020 Category: Genetics & Stem Cells Authors: Carthew RW, Shyer A Tags: Curr Opin Genet Dev Source Type: research

The dawn of non-human primate models for neurodevelopmental disorders.
Abstract Non-human primates (NHPs) have been proposed as good models for neurodevelopmental disorders due to close similarities to humans in terms of brain structure and cognitive function. The recent development of genome editing technologies has opened new avenues to generate and investigate genetically modified NHPs as models for human disorders. Here, we review the early successes of genetic NHP models for neurodevelopmental disorders and further discuss the technological challenges and opportunities to create next generation NHP models with more sophisticated genetic manipulation and faithful representations ...
Source: Current Opinion in Genetics and Development - July 17, 2020 Category: Genetics & Stem Cells Authors: Aida T, Feng G Tags: Curr Opin Genet Dev Source Type: research

Human evolutionary history in Eastern Eurasia using insights from ancient DNA.
Abstract Advances in ancient genomics are providing unprecedented insight into modern human history. Here, we review recent progress uncovering prehistoric populations in Eastern Eurasia based on ancient DNA studies from the Upper Pleistocene to the Holocene. Many ancient populations existed during the Upper Pleistocene of Eastern Eurasia-some with no substantial ancestry related to present-day populations, some with an affinity to East Asians, and some who contributed to Native Americans. By the Holocene, the genetic composition across East Asia greatly shifted, with several substantial migrations. Three are sout...
Source: Current Opinion in Genetics and Development - July 16, 2020 Category: Genetics & Stem Cells Authors: Zhang M, Fu Q Tags: Curr Opin Genet Dev Source Type: research

Cortico-basal ganglia circuits underlying dysfunctional control of motor behaviors in neuropsychiatric disorders.
Abstract Neuropsychiatric disorders often manifest with abnormal control of motor behavior. Common symptoms include restricted and repetitive patterns of behavior (RRBs). Cortico-basal ganglia circuits have been implicated in the etiology of RBBs. However, there is a vast range of behaviors encompassed in RRBs, from simple explosive motor tics to rather complex ritualized compulsions. In this review, we highlight how recent findings about the function of specific basal ganglia circuits can begin to shed light into defined motor symptoms associated with neuropsychiatric disorders. We discuss recent studies using ge...
Source: Current Opinion in Genetics and Development - July 15, 2020 Category: Genetics & Stem Cells Authors: Vicente AM, Martins GJ, Costa RM Tags: Curr Opin Genet Dev Source Type: research

Lessons from single cell sequencing in CNS cell specification and function.
Abstract Modern RNA sequencing methods have greatly increased our understanding of the molecular fingerprint of neurons, astrocytes and oligodendrocytes throughout the central nervous system (CNS). Technical approaches with greater sensitivity and throughput have uncovered new connections between gene expression, cell biology, and ultimately CNS function. In recent years, single cell RNA-sequencing (scRNA-seq) has made a large impact on the neurosciences by enhancing the resolution of types of cells that make up the CNS and shedding light on their developmental trajectories and how their diversity is modified acro...
Source: Current Opinion in Genetics and Development - July 13, 2020 Category: Genetics & Stem Cells Authors: Li Z, Tyler WA, Haydar TF Tags: Curr Opin Genet Dev Source Type: research

The role of clustered protocadherins in neurodevelopment and neuropsychiatric diseases.
Abstract During development, individual neurons extend highly branched arbors that innervate the surrounding territory, enabling the formation of appropriate synaptic connections. The clustered protocadherins (cPCDH), a family of diverse cell-surface homophilic proteins, provide each neuron with a cell specific identity required for distinguishing between self versus non-self. While only 52 unique cPcdh isoforms are encoded in the human genome, a combination of stochastic promoter choice and the formation of a protein lattice through engagement of adjacent cPCDH protein cis/trans-tetramers confer the high degree o...
Source: Current Opinion in Genetics and Development - July 13, 2020 Category: Genetics & Stem Cells Authors: Flaherty E, Maniatis T Tags: Curr Opin Genet Dev Source Type: research

Experimental embryology of gastrulation: pluripotent stem cells as a new model system.
Abstract Gastrulation is an inherently complicated process involving a well-orchestrated series of collective cellular behaviours that lead to the emergence of the body plan of the organism. A convenient method to explore the mechanical and chemical interactions that underpin this process, is to isolate specific tissues and to allow them to develop in isolation or in a novel environment. These approaches are the essence of experimental embryology and have enabled an understanding of the underlying principles of embryogenesis, in a way that observation alone could not. The recent rise of 3D culture systems using Em...
Source: Current Opinion in Genetics and Development - July 10, 2020 Category: Genetics & Stem Cells Authors: Moris N, Martinez Arias A, Steventon B Tags: Curr Opin Genet Dev Source Type: research

Molecular mechanisms for targeted ASD treatments.
Abstract The possibility to generate construct valid animal models enabled the development and testing of therapeutic strategies targeting the core features of autism spectrum disorders (ASDs). At the same time, these studies highlighted the necessity of identifying sensitive developmental time windows for successful therapeutic interventions. Animal and human studies also uncovered the possibility to stratify the variety of ASDs in molecularly distinct subgroups, potentially facilitating effective treatment design. Here, we focus on the molecular pathways emerging as commonly affected by mutations in diverse ASD-...
Source: Current Opinion in Genetics and Development - July 9, 2020 Category: Genetics & Stem Cells Authors: Basilico B, Morandell J, Novarino G Tags: Curr Opin Genet Dev Source Type: research

The history behind the mosaic of the Americas.
Abstract Focusing on literature published in 2018-2020, we review inferences about: (i) how ancient DNA is contributing to clarify the peopling of the Americas and the dispersal of its first inhabitants, (ii) how the interplay between environmental diversity and culture has influenced the genetic structure and adaptation of Andean and Amazon populations, (iii) how genetics has contributed to our understanding of the Pre-Columbian Tupi expansion in Eastern South America, (iv) the subcontinental origins and dynamics of Post-Columbian admixture in the Americas, and finally, (v) episodes of adaptive natural selection ...
Source: Current Opinion in Genetics and Development - July 9, 2020 Category: Genetics & Stem Cells Authors: Mendes M, Alvim I, Borda V, Tarazona-Santos E Tags: Curr Opin Genet Dev Source Type: research

Expanded potential: the key to synthetic embryo?
Abstract How does an embryo acquire totipotency and develop into an adult is a fundamental scientific question. Stem cells derived from pre-implantation embryos or reprogrammed from somatic cells with totipotency features have been established. They have enriched molecular features, including transcription, epigenetic modification, chromatin structure and metabolism, similar to early embryos from 2 cell (2C) to morula. Functionally, they display a broader developmental potential to differentiate into cell types in the embryonic and extraembryonic tissues. The expanded developmental potential was further demonstrat...
Source: Current Opinion in Genetics and Development - July 8, 2020 Category: Genetics & Stem Cells Authors: Yang J, Fu H, Tam C, Liu P Tags: Curr Opin Genet Dev Source Type: research

Functional genomics links genetic origins to pathophysiology in neurodegenerative and neuropsychiatric disease.
Abstract Neurodegenerative and neuropsychiatric disorders are pervasive and debilitating conditions characterized by diverse clinical syndromes and comorbidities, whose origins are as complex and heterogeneous as their associated phenotypes. Risk for these disorders involves substantial genetic liability, which has fueled large-scale genetic studies that have led to a flood of discoveries. In turn, these discoveries have exposed substantial gaps in our knowledge with regards to the complicated genetic architecture of each disorder and the substantial amount of genetic overlap among disorders, which implies some de...
Source: Current Opinion in Genetics and Development - July 3, 2020 Category: Genetics & Stem Cells Authors: Wamsley B, Geschwind DH Tags: Curr Opin Genet Dev Source Type: research

Evolution of the mutation rate across primates.
Abstract Germline mutations are the source of all heritable variation. In the past few years, whole genome sequencing has allowed direct and comprehensive surveys of mutation patterns in humans and other species. These studies have documented substantial variation in both mutation rates and spectra across primates, the causes of which remain unclear. Here, we review what is currently known about mutation rates in primates, highlight the factors proposed to explain the variation across species, and discuss some implications of these findings on our understanding of the chronology of primate evolution and the proces...
Source: Current Opinion in Genetics and Development - July 3, 2020 Category: Genetics & Stem Cells Authors: Chintalapati M, Moorjani P Tags: Curr Opin Genet Dev Source Type: research

Branching out: what omics can tell us about primate evolution.
Abstract The study of primate comparative genomics has long been a focus of research, particularly in the context of understanding human evolutionary history. Recently, high-throughput methods have become accessible that allow us to tackle these questions at scale by comparing genomes within and between species, or looking at gene regulatory and expression changes between species and tissues. This burst in large-scale genomic studies has drastically increased the resolution at which we are now able to understand the evolutionary forces acting upon our own species. Furthermore, the drop in sequencing costs has made...
Source: Current Opinion in Genetics and Development - July 3, 2020 Category: Genetics & Stem Cells Authors: Kuderna LF, Esteller-Cucala P, Marques-Bonet T Tags: Curr Opin Genet Dev Source Type: research

Engineering and modeling of multicellular morphologies and patterns.
Abstract Synthetic multicellular (MC) systems have the capacity to increase our understanding of biofilms and higher organisms, and to serve as engineering platforms for developing complex products in the areas of medicine, biosynthesis and smart materials. Here we provide an interdisciplinary perspective and review on emerging approaches to engineer and model MC systems. We lay out definitions for key terms in the field and identify toolboxes of standardized parts which can be combined into various MC algorithms to achieve specific outcomes. Many essential parts and algorithms have been demonstrated in some form....
Source: Current Opinion in Genetics and Development - July 2, 2020 Category: Genetics & Stem Cells Authors: Kim H, Jin X, Glass DS, Riedel-Kruse IH Tags: Curr Opin Genet Dev Source Type: research

The evolution of the human brain and disease susceptibility.
Abstract Evolutionary perspective is critical for understanding human biology, human medicine, and the traits that make human beings unique. One of the crucial characteristics that sets humans apart from other extant species is our cognitive ability, which allows for complex processes including symbolic thought, theory of mind, and syntactical-grammatical language, and is thought to arise from the expansion and specialization of the human nervous system. It has been hypothesized that the same evolutionary changes that allowed us to develop these valuable skills made humans susceptible to neurodevelopmental and neu...
Source: Current Opinion in Genetics and Development - July 2, 2020 Category: Genetics & Stem Cells Authors: Pattabiraman K, Muchnik SK, Sestan N Tags: Curr Opin Genet Dev Source Type: research

Single cell genomics and developmental biology: moving beyond the generation of cell type catalogues.
s B Abstract Major developmental processes such as gastrulation and early embryogenesis rely on a complex network of cell-cell interactions, chromatin remodeling, and transcriptional regulators. This makes it challenging to study early development when using bulk populations of cells. Recent advances in single-cell technologies have allowed researchers to better understand the interactions between different molecular modalities and the heterogeneities within classically defined cell types. As new single-cell technologies mature, they have the potential of providing a step-change in our understanding of embryogenes...
Source: Current Opinion in Genetics and Development - July 2, 2020 Category: Genetics & Stem Cells Authors: Ton MN, Guibentif C, Göttgens B Tags: Curr Opin Genet Dev Source Type: research

Nucleic acid therapeutics in neurodevelopmental disease.
Abstract Nucleic acid therapeutics allow sequence-based targeting of mutation-harboring genes. They can be used to increase the expression and function of disease genes or to decrease the expression of toxic gene products. Antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), and gene-replacement therapies have received FDA approval, and in vivo gene editing applications are currently under development. Special consideration should be given to target engagement in neurons and amelioration of neurological phenotypes. Here we discuss the uses and limitations of different nucleic acid therapeutics, high...
Source: Current Opinion in Genetics and Development - July 1, 2020 Category: Genetics & Stem Cells Authors: Winkelsas AM, Fischbeck KH Tags: Curr Opin Genet Dev Source Type: research

Genetic pathways involved in human speech disorders.
Abstract Rare genetic variants that disrupt speech development provide entry points for deciphering the neurobiological foundations of key human capacities. The value of this approach is illustrated by FOXP2, a transcription factor gene that was implicated in speech apraxia, and subsequently investigated using human cell-based systems and animal models. Advances in next-generation sequencing, coupled to de novo paradigms, facilitated discovery of etiological variants in additional genes in speech disorder cohorts. As for other neurodevelopmental syndromes, gene-driven studies show blurring of boundaries between di...
Source: Current Opinion in Genetics and Development - June 30, 2020 Category: Genetics & Stem Cells Authors: den Hoed J, Fisher SE Tags: Curr Opin Genet Dev Source Type: research

The role of somatic mosaicism in brain disease.
Abstract In this review we discuss the importance of genetic somatic mosaicism and its impact on brain diseases. We start from introducing the different types of somatic mutations, their frequencies and abundances across development and lifespan. We then describe how weakness in DNA repair mechanisms influences their prevalence. Finally, we address their functional consequences in the brain and review recent research showing their unsuspected importance in several neurodevelopmental, psychiatric, and neurodegenerative diseases. PMID: 32622340 [PubMed - as supplied by publisher] (Source: Current Opinion in Gen...
Source: Current Opinion in Genetics and Development - June 30, 2020 Category: Genetics & Stem Cells Authors: Jourdon A, Fasching L, Scuderi S, Abyzov A, Vaccarino FM Tags: Curr Opin Genet Dev Source Type: research

Inferring evolutionary dynamics of mutation rates through the lens of mutation spectrum variation.
Abstract There are many possible failure points in the transmission of genetic information that can produce heritable germline mutations. Once a mutation has been passed from parents to offspring for several generations, it can be difficult or impossible to identify its root cause; however, sometimes the nature of the ancestral and derived DNA sequences can provide mechanistic clues about a genetic change that happened hundreds or thousands of generations ago. Here, we review evidence that the sequence context 'spectrum' of germline mutagenesis has been evolving surprisingly rapidly over the history of humans and ...
Source: Current Opinion in Genetics and Development - June 29, 2020 Category: Genetics & Stem Cells Authors: Carlson J, DeWitt WS, Harris K Tags: Curr Opin Genet Dev Source Type: research

Update on M üller glia regenerative potential for retinal repair.
Update on Müller glia regenerative potential for retinal repair. Curr Opin Genet Dev. 2020 Jun 30;64:52-59 Authors: García-García D, Locker M, Perron M Abstract Retinal regeneration efficiency from Müller glia varies tremendously among vertebrate species, being extremely limited in mammals. Efforts towards the identification of molecular mechanisms underlying Müller cell proliferative and neurogenic potential should help finding strategies to awake them and ensure regeneration in mammals. We provide here an update on the most recent and original progresses made in the fiel...
Source: Current Opinion in Genetics and Development - June 29, 2020 Category: Genetics & Stem Cells Authors: García-García D, Locker M, Perron M Tags: Curr Opin Genet Dev Source Type: research

Xeno-organ donor pigs with multiple genetic modifications - the more the better?
Abstract The number of donated human organs and tissues for patients with terminal organ failure falls far short of the need. Alternative sources, such as organs and tissues from animals, are therefore urgently required. During the past few years, major progress has been made in the development of genetically multi-modified donor pigs, and their organs have been shown to be safe and efficacious in life-supporting transplantation models into non-human primates, paving the way to clinical xenotransplantation studies. Here, we summarize recent developments in pig genome engineering and discuss efforts to develop the ...
Source: Current Opinion in Genetics and Development - June 29, 2020 Category: Genetics & Stem Cells Authors: Kemter E, Schnieke A, Fischer K, Cowan PJ, Wolf E Tags: Curr Opin Genet Dev Source Type: research

Poison exons in neurodevelopment and disease.
Abstract Poison exons are naturally occurring, highly conserved alternative exons that contain a premature termination codon. Inclusion of a poison exon in a transcript targets the transcript for nonsense mediated decay, decreasing the amount of protein produced. Poison exons are proposed to play an important role in tissue-specific expression, development and autoregulation of gene expression. Recently, several studies that performed systematic investigations of alternative splicing in the brain have highlighted the abundance of transcripts containing poison exons, some of which are spliced in a cell type-specifi...
Source: Current Opinion in Genetics and Development - June 28, 2020 Category: Genetics & Stem Cells Authors: Carvill GL, Mefford HC Tags: Curr Opin Genet Dev Source Type: research

Archaic hominin genomics provides a window into gene expression evolution.
Abstract Differences in gene expression are thought to account for most phenotypic differences within and between species. Consequently, gene expression is a powerful lens through which to study divergence between modern humans and our closest evolutionary relatives, the Neanderthals and Denisovans. Such insights complement biological knowledge gleaned from the fossil record, while also revealing general features of the mode and tempo of regulatory evolution. Because of the degradation of ancient RNA, gene expression profiles of archaic hominins must be studied by indirect means. As such, conclusions drawn from th...
Source: Current Opinion in Genetics and Development - June 28, 2020 Category: Genetics & Stem Cells Authors: Yan SM, McCoy RC Tags: Curr Opin Genet Dev Source Type: research

Latest trends in archaeogenetic research of west Eurasians.
Abstract During the past ten years, archaeogenetic research has exponentially grown to study the genetic history of human populations, using genome-wide data from large numbers of ancient individuals. Of the entire globe, Europe and the Near East are the regions where ancient DNA data is by far most abundant with over 2500 genomes published at present. In this review, we focus on archaeological contexts that have received less attention in the literature, specifically those associated with west Eurasian hunter-gatherers as well as populations from the Iron Age and later historical periods. In addition, we emphasiz...
Source: Current Opinion in Genetics and Development - June 27, 2020 Category: Genetics & Stem Cells Authors: Olalde I, Posth C Tags: Curr Opin Genet Dev Source Type: research

Neural circuit reorganisation after spinal cord injury in zebrafish.
Abstract Spinal cord injuries disrupt signalling from the brain leading to loss of limb, locomotion, sexual and bladder function, usually irreversible in humans. In zebrafish, recovery of function occurs in a few days for larvae or a few weeks for adults due to regrowth of axons and de novo neurogenesis. Together with its genetic amenability and optical clarity, this makes zebrafish a powerful animal model to study circuit reorganisation after spinal cord injuries. With the fast evolution of techniques, we can forecast significative improvements of our knowledge of the mechanisms leading to successful or failed re...
Source: Current Opinion in Genetics and Development - June 26, 2020 Category: Genetics & Stem Cells Authors: El-Daher F, Becker CG Tags: Curr Opin Genet Dev Source Type: research

The importance of including ethnically diverse populations in studies of quantitative trait evolution.
Abstract For many traits, human variation is less a matter of categorical differences than quantitative variation, such as height, where individuals fall along a continuum from short to tall. Most recent studies utilize large population-based samples with whole-genome sequences to study the evolution of these traits and have made significant progress implementing a broad spectrum of techniques. However, relatively few studies of quantitative trait evolution include ethnically diverse populations, which often harbor the highest levels of genetic and phenotypic diversity. Thus, our ability to draw inferences about q...
Source: Current Opinion in Genetics and Development - June 26, 2020 Category: Genetics & Stem Cells Authors: McQuillan MA, Zhang C, Tishkoff SA, Platt A Tags: Curr Opin Genet Dev Source Type: research

Linking genotype, cell behavior, and phenotype: multidisciplinary perspectives with a basis in zebrafish patterns.
Abstract Zebrafish are characterized by dark and light stripes, but mutants display a rich variety of altered patterns. These patterns arise from the interactions of brightly colored pigment cells, making zebrafish a self-organization problem. The diversity of patterns present in zebrafish and other emerging fish models provides an excellent system for elucidating how genes, cell behavior, and visible animal characteristics are related. With the goal of highlighting how experimental and mathematical approaches can be used to link these scales, I overview current descriptions of zebrafish patterning, describe advan...
Source: Current Opinion in Genetics and Development - June 26, 2020 Category: Genetics & Stem Cells Authors: Volkening A Tags: Curr Opin Genet Dev Source Type: research

Adaptive viscoelasticity of epithelial cell junctions: from models to methods.
Abstract Epithelial morphogenesis relies on constituent cells' ability to finely tune their mechanical properties. Resulting elastic-like and viscous-like behaviors arise from mechanochemical signaling coordinated spatiotemporally at cell-cell interfaces. Direct measurement of junction rheology can mechanistically dissect mechanical deformations and their molecular origins. However, the physical basis of junction viscoelasticity has only recently become experimentally tractable. Pioneering studies have uncovered exciting findings on the nature of contractile forces and junction deformations, inspiring a fundamenta...
Source: Current Opinion in Genetics and Development - June 26, 2020 Category: Genetics & Stem Cells Authors: Cavanaugh KE, Staddon MF, Banerjee S, Gardel ML Tags: Curr Opin Genet Dev Source Type: research

Perspectives on somatic reprogramming: spotlighting epigenetic regulation and cellular heterogeneity.
Abstract Induction of pluripotency in somatic cells via ectopic expression of defined factors demonstrates the reversibility of developmental programming, thus serves as an ideal model to investigate the underlying principles of cell fate determination, which drives the differentiation of various cell types from an identical genome. Over the last decade, our understanding has grown considerably regarding how somatic reprogramming initiates and be regulated. Recent mechanistic investigations on chromatin architecture regulation and cell heterogeneity significantly contribute to the understanding of somatic reprogra...
Source: Current Opinion in Genetics and Development - June 25, 2020 Category: Genetics & Stem Cells Authors: Chen J Tags: Curr Opin Genet Dev Source Type: research

A cell in hand is worth two in the embryo: recent advances in 2-cell like cell reprogramming.
Abstract Multicellular organisms develop from a single cell, the zygote. This feature is referred to as totipotency. In the mouse, only the zygote and the 2-cell stage embryo display this attribute. Cells resembling the embryonic 2-cell stage blastomeres were identified in embryonic stem (ES) cell cultures as '2-cell-like cells' (2CLCs). This discovery brought the first cellular model with the possibility to investigate some features of the totipotent embryo and the molecular mechanisms regulating totipotency in vitro. In this article, we discuss the latest advancements on the research on 2CLCs, which have uncover...
Source: Current Opinion in Genetics and Development - June 25, 2020 Category: Genetics & Stem Cells Authors: Iturbide A, Torres-Padilla ME Tags: Curr Opin Genet Dev Source Type: research

Regeneration in the spiny mouse, Acomys, a new mammalian model.
We describe the tissues and organs that show exceptional regenerative ability following injury in the spiny mouse, Acomys. The skin and ear regenerate: hair and its associated stem cell niches, sebaceous glands, dermis, adipocytes, cartilage, smooth muscle, and skeletal muscle. Internal tissues such as the heart, kidney, muscle, and spinal cord respond to damage by showing significantly reduced inflammation and improved regeneration responses. The reason for this improved ability may lie in the immune system which shows a blunted inflammatory response to injury compared to that of the typical mammal, but we also show that ...
Source: Current Opinion in Genetics and Development - June 25, 2020 Category: Genetics & Stem Cells Authors: Sandoval AGW, Maden M Tags: Curr Opin Genet Dev Source Type: research

Recent insights into zebrafish cardiac regeneration.
der N Abstract In humans, myocardial infarction results in ventricular remodeling, progressing ultimately to cardiac failure, one of the leading causes of death worldwide. In contrast to the adult mammalian heart, the zebrafish model organism has a remarkable regenerative capacity, offering the possibility to research the bases of natural regeneration. Here, we summarize recent insights into the cellular and molecular mechanisms that govern cardiac regeneration in the zebrafish. PMID: 32599303 [PubMed - as supplied by publisher] (Source: Current Opinion in Genetics and Development)
Source: Current Opinion in Genetics and Development - June 25, 2020 Category: Genetics & Stem Cells Authors: Sanz-Morejón A, Mercader N Tags: Curr Opin Genet Dev Source Type: research

Gene constraint and genotype-phenotype correlations in neurodevelopmental disorders.
Abstract With the advent and widespread adoption of high-throughput DNA sequencing, genetic discoveries in neurodevelopmental disorders (NDDs) are advancing very rapidly. The identification of novel NDD genes and of rare, highly penetrant pathogenic variants is leading to improved understanding of genotype-phenotype correlations. Here we emphasize the importance of large-scale, reference databases such as gnomAD to determine gene and variant level constraints and facilitate gene discovery, variant interpretation, and genotype-phenotype correlations. While the majority of dominant NDD genes are highly intolerant to...
Source: Current Opinion in Genetics and Development - June 25, 2020 Category: Genetics & Stem Cells Authors: Betancur C, Buxbaum JD Tags: Curr Opin Genet Dev Source Type: research

The frontiers of sequencing in undiagnosed neurodevelopmental diseases.
Abstract Characterized by impairments in brain and central nervous system development, neurodevelopmental diseases causes are highly heterogeneous. Although many of these diseases are individually rare, collectively more than 3% of the children are reported to be affected with a type of neurodevelopmental diseases worldwide, and many remain undiagnosed even with current genomic tools. Identifying the genetic causes of these diseases allows better clinical management and expands our understanding of human neurodevelopment. Over the past decade, expansion of genomic sequencing and some methodologic improvements have...
Source: Current Opinion in Genetics and Development - June 25, 2020 Category: Genetics & Stem Cells Authors: Lee H, Nelson SF Tags: Curr Opin Genet Dev Source Type: research

Activity regulates brain development in the fly.
Abstract It has long been appreciated that activity sculpts the formation of neuronal circuits in the mammalian brain. By contrast, in Drosophila it was generally thought that genetically hardwired mechanisms of development, mediated by cell recognition molecules, are sufficient to specify the connectome-the complex and stereotyped pattern of connections between neurons. Here, we consider recent findings that activity during development also contributes to circuit assembly in the fly. These observations suggest that activity is a fundamental aspect of brain development in general. They also highlight the opportuni...
Source: Current Opinion in Genetics and Development - June 24, 2020 Category: Genetics & Stem Cells Authors: Akin O, Zipursky SL Tags: Curr Opin Genet Dev Source Type: research