Neurodevelopmental deficits and cell-type-specific transcriptomic perturbations in a mouse model of < i > HNRNPU < /i > haploinsufficiency
by Sarah A. Dugger, Ryan S. Dhindsa, Gabriela De Almeida Sampaio, Andrew K. Ressler, Elizabeth E. Rafikian, Sabrina Petri, Verity A. Letts, JiaJie Teoh, Junqiang Ye, Sophie Colombo, Yueqing Peng, Mu Yang, Michael J. Boland, Wayne N. Frankel, David B. Goldstein
Heterozygousde novo loss-of-function mutations in the gene expression regulatorHNRNPU cause an early-onset developmental and epileptic encephalopathy. To gain insight into pathological mechanisms and lay the potential groundwork for developing targeted therapies, we characterized the neurophysiologic and cell-type-specific transcriptomic consequences of a mouse mode...
Source: PLoS Genetics - October 2, 2023 Category: Genetics & Stem Cells Authors: Sarah A. Dugger Source Type: research
Genome-wide single-molecule analysis of long-read DNA methylation reveals heterogeneous patterns at heterochromatin that reflect nucleosome organisation
by Lyndsay Kerr, Ioannis Kafetzopoulos, Ramon Grima, Duncan Sproul
High-throughput sequencing technology is central to our current understanding of the human methylome. The vast majority of studies use chemical conversion to analyse bulk-level patterns of DNA methylation across the genome from a population of cells. While this technology has been used to probe single-molecule methylation patterns, such analyses are limited to short reads of a few hundred basepairs. DNA methylation can also be directly detected using Nanopore sequencing which can generate reads measuring megabases in length. However, thus far these analyse...
Source: PLoS Genetics - October 2, 2023 Category: Genetics & Stem Cells Authors: Lyndsay Kerr Source Type: research
Microtubules oppose cortical actomyosin-driven membrane ingression during < i > C < /i > . < i > elegans < /i > meiosis I polar body extrusion
by Alyssa R. Quiogue, Eisuke Sumiyoshi, Adam Fries, Chien-Hui Chuang, Bruce Bowerman
DuringC.elegans oocyte meiosis I cytokinesis and polar body extrusion, cortical actomyosin is locally remodeled to assemble a contractile ring that forms within and remains part of a much larger and actively contractile cortical actomyosin network. This network both mediates contractile ring dynamics and generates shallow ingressions throughout the oocyte cortex during polar body extrusion. Based on our analysis of requirements for CLS-2, a member of the CLASP family of proteins that stabilize microtubules, we recently proposed that a bal...
Source: PLoS Genetics - October 2, 2023 Category: Genetics & Stem Cells Authors: Alyssa R. Quiogue Source Type: research
Adenylosuccinate lyase deficiency affects neurobehavior via perturbations to tyramine signaling in < i > Caenorhabditis elegans < /i >
by Corinna A. Moro, Sabrina A. Sony, Latisha P. Franklin, Shirley Dong, Mia M. Peifer, Kathryn E. Wittig, Wendy Hanna-Rose
Adenylosuccinate lyase deficiency is an ultrarare congenital metabolic disorder associated with muscle weakness and neurobehavioral dysfunction. Adenylosuccinate lyase is required forde novo purine biosynthesis, acting twice in the pathway at non-sequential steps. Genetic models can contribute to our understanding of the etiology of disease phenotypes and pave the way for development of therapeutic treatments. Here, we establish the first model to specifically study neurobehavioral aspects of adenylos...
Source: PLoS Genetics - September 29, 2023 Category: Genetics & Stem Cells Authors: Corinna A. Moro Source Type: research
A double-negative feedback loop between miR319c and JAW-TCPs establishes growth pattern in incipient leaf primordia in < i > Arabidopsis thaliana < /i >
by Naveen Shankar, Preethi Sunkara, Utpal Nath
The microRNA miR319 and its target JAW-TCP transcription factors regulate the proliferation-to-differentiation transition of leaf pavement cells in diverse plant species. In young Arabidopsis leaf primordia,JAW-TCPs are detected towards the distal region whereas the major mRNA319-encoding geneMIR319C, is expressed at the base. Little is known about how this complementary expression pattern ofMIR319C andJAW-TCPs is generated. Here, we show thatMIR319C is initially expressed uniformly throughout the incipient primordia and is later abruptly down-regulated at the distal region, ...
Source: PLoS Genetics - September 28, 2023 Category: Genetics & Stem Cells Authors: Naveen Shankar Source Type: research
RBMX involves in telomere stability maintenance by regulating TERRA expression
In this study, we report that the RNA binding protein RBMX is a novel regulator of TERRA level and telomere integrity. The expression level of TERRA is significantly elevated in RBMX depleted cells, leading to enhanced telomere R-loop formation, replication stress, and telomere instability. We also found that RBMX binds to TERRA and the nuclear exosome targeting protein ZCCHC8 simultaneously, and that TERRA degradation slows down upon RBMX depletion, implying that RBMX promotes TERRA degradation by regulating its transportation to the nuclear exosome, which decays nuclear RNAs. Altogether, these findings uncover a new role...
Source: PLoS Genetics - September 27, 2023 Category: Genetics & Stem Cells Authors: Jingfan Liu Source Type: research
A digital twin reproducing gene regulatory network dynamics of early < i > Ciona < /i > embryos indicates robust buffers in the network
by Miki Tokuoka, Yutaka Satou
How gene regulatory networks (GRNs) encode gene expression dynamics and how GRNs evolve are not well understood, although these problems have been studied extensively. We created a digital twin that accurately reproduces expression dynamics of 13 genes that initiate expression in 32-cell ascidian embryos. We first showed that gene expression patterns can be manipulated according to predictions by this digital model. Next, to simulate GRN rewiring, we changed regulatory functions that represented their regulatory mechanisms in the digital twin, and found that in 55 of 100 cases, removal of a s...
Source: PLoS Genetics - September 27, 2023 Category: Genetics & Stem Cells Authors: Miki Tokuoka Source Type: research
Correction: A role for brassinosteroid signalling in decision-making processes in the Arabidopsis seedling
by Nils Kalbfu ß, Alexander Strohmayr, Marcel Kegel, Lien Le, Friederike Grosse-Holz, Barbara Brunschweiger, Katharina Stöckl, Christian Wiese, Carina Franke, Caroline Schiestl, Sophia Prem, Shuyao Sha, Katrin Franz-Oberdorf, Juliane Hafermann, Marc Thiemé, Eva Facher, Wojciech Palubicki, Cordelia Bolle, Farhah F. Assaad (Source: PLoS Genetics)
Source: PLoS Genetics - September 27, 2023 Category: Genetics & Stem Cells Authors: Nils Kalbfu ß Source Type: research
Notch pathway mutants do not equivalently perturb mouse embryonic retinal development
by Bernadett Bosze, Julissa Suarez-Navarro, Illiana Cajias, Joseph A. Brzezinski IV, Nadean L. Brown
In the vertebrate eye, Notch ligands, receptors, and ternary complex components determine the destiny of retinal progenitor cells in part by regulatingHes effector gene activity. There are multiple paralogues for nearly every node in this pathway, which results in numerous instances of redundancy and compensation during development. To dissect such complexity at the earliest stages of eye development, we used seven germline or conditional mutant mice and two spatiotemporally distinct Cre drivers. We perturbed the Notch ter...
Source: PLoS Genetics - September 26, 2023 Category: Genetics & Stem Cells Authors: Bernadett Bosze Source Type: research
Chromatin accessibility, not 5mC methylation covaries with partial dosage compensation in crows
by Ana Catal án, Justin Merondun, Ulrich Knief, Jochen B. W. Wolf
The evolution of genetic sex determination is often accompanied by degradation of the sex-limited chromosome. Male heterogametic systems have evolved convergent, epigenetic mechanisms restoring the resulting imbalance in gene dosage between diploid autosomes (AA) and the hemizygous sex chromosome (X). Female heterogametic systems (AAf Zf, AAm ZZm) tend to only show partial dosage compensation (0.5 (Source: PLoS Genetics)
Source: PLoS Genetics - September 25, 2023 Category: Genetics & Stem Cells Authors: Ana Catal án Source Type: research
H4K20me3 is important for Ash1-mediated H3K36me3 and transcriptional silencing in facultative heterochromatin in a fungal pathogen
by Mareike M öller, John B. Ridenour, Devin F. Wright, Faith A. Martin, Michael Freitag
Facultative heterochromatin controls development and differentiation in many eukaryotes. In metazoans, plants, and many filamentous fungi, facultative heterochromatin is characterized by transcriptional repression and enrichment with nucleosomes that are trimethylated at histone H3 lysine 27 (H3K27me3). While loss of H3K27me3 results in derepression of transcriptional gene silencing in many species, additional up- and downstream layers of regulation are necessary to mediate control of transcription in chromosome regions enriched with ...
Source: PLoS Genetics - September 25, 2023 Category: Genetics & Stem Cells Authors: Mareike M öller Source Type: research
Human genetic adaptation related to cellular zinc homeostasis
by Ana Roca-Umbert, Jorge Garcia-Calleja, Marina Vogel-Gonz ález, Alejandro Fierro-Villegas, Gerard Ill-Raga, Víctor Herrera-Fernández, Anja Bosnjak, Gerard Muntané, Esteban Gutiérrez, Felix Campelo, Rubén Vicente, Elena BoschSLC30A9 encodes a ubiquitously zinc transporter (ZnT9) and has been consistently suggested as a candidate for positive selection in humans. However, no direct adaptive molecular phenotype has been demonstrated. Our results provide evidence for directional selection operating in two major complementary haplotypes in Africa and East Asia. These haplotypes are associated with differential gene expr...
Source: PLoS Genetics - September 25, 2023 Category: Genetics & Stem Cells Authors: Ana Roca-Umbert Source Type: research
Spatial regulation of Drosophila ovarian Follicle Stem Cell division rates and cell cycle transitions
by David Melamed, Aaron Choi, Amy Reilein, Simon Tavar é, Daniel Kalderon
Drosophila ovarian Follicle Stem Cells (FSCs) present a favorable paradigm for understanding how stem cell division and differentiation are balanced in communities where those activities are independent. FSCs also allow exploration of how this balance is integrated with spatial stem cell heterogeneity. Posterior FSCs become proliferative Follicle Cells (FCs), while anterior FSCs become quiescent Escort Cells (ECs) at about one fourth the frequency. A single stem cell can nevertheless produce both FCs and ECs because it can move between anterior and...
Source: PLoS Genetics - September 25, 2023 Category: Genetics & Stem Cells Authors: David Melamed Source Type: research
TDP-43 pathology in < i > Drosophila < /i > induces glial-cell type specific toxicity that can be ameliorated by knock-down of SF2/SRSF1
We report that TDP-43 pathology inDrosophila is sufficient to cause progressive loss of each of the 5 glial sub-types. But the effects on organismal survival were most pronounced when TDP-43 pathology was induced in the perineural glia (PNG) or astrocytes. In the case of PNG, this effect is not attributable to loss of the glial population, because ablation of these glia by expression of pro-apoptotic reaper expression has relatively little impact on survival. To uncover underlying mechanisms, we used cell-type-specific nuclear RNA sequencing to characterize the transcriptional changes induced by pathological TDP-43 express...
Source: PLoS Genetics - September 25, 2023 Category: Genetics & Stem Cells Authors: Sarah Krupp Source Type: research
Large-scale whole exome sequencing studies identify two genes, < i > CTSL < /i > and < i > APOE < /i > , associated with lung cancer
In this study, we investigate the contribution of rare variants (RVs) (minor allele frequency (Source: PLoS Genetics)
Source: PLoS Genetics - September 22, 2023 Category: Genetics & Stem Cells Authors: Jingxiong Xu Source Type: research
