Biology subjects

Wu, H.

Publications and source records attributed to Wu, H..

At least 415 records · Page 23Linked to original sources

bioRxiv2021

Intracellular glycosyl hydrolase PslG shapes bacterial cell fate, signaling, and the biofilm development of Pseudomonas aeruginosa

Biofilm formation is one of most important causes leading to persistent infections. Exopolysaccharides are usually a main component of biofilm matrix. Genes encoding for glycosyl hydrolases are often found in gene clusters that are involved in the exopolysaccharide synthesis. It remains elusive about the functions of intracellular glycosyl hydrolase and why a polysaccharide synthesis gene cluster requires a glycosyl hydrolase. Here we systematically studied the role of intracellular PslG, a glycosyl hydrolase that is co-transcribed with 15 psl genes, which is responsible for the synthesis of exopolysaccharide Psl (ePsl), a key biofilm matrix polysaccharide in opportunistic pathogen Pseudomonas aeruginosa. We showed that lacking of PslG in this opportunistic pathogen alters the signaling function and structure of ePsl, changes the relative level of cyclic-di-GMP within daughter cells during cell division and shapes the localization of ePsl on bacterial periphery, thus results in long chains of bacterial cells, fast-forming and compact biofilm microcolonies. Our results reveal the important roles of intracellular PslG on the cell fate and biofilm development.

microbiology↗

bioRxiv2021

Fully Human Antibody Immunoglobulin from Transchromosomic Bovines is Potent Against SARS-CoV-2 Variant Pseudoviruses

SAB-185 is a fully human polyclonal anti-SARS-CoV-2 immunoglobulin produced from the plasma of transchromosomic bovines that are hyperimmunized with recombinant SARS-CoV-2 Wuhan-Hu-1 Spike protein. SAB-185 is being evaluated for efficacy in aphase 3 clinical trial. The World Health Organization (WHO) has identified multiple Variants-of-Concern and Variants-of-Interest (VOC/VOI) that have mutations in their Spike protein that appear to increase transmissibility and/or reduce the effectiveness of therapeutics and vaccines, among other parameters of concern. SAB-185 was evaluated using lentiviral-based pseudovirus assays performed in a BSL2 environment that incorporates stable or transient cell lines that express human angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). The results indicate that SAB-185 retained neutralization potency against multiple SARS-CoV-2 pseudovirus variants, including the Delta, Kappa, Lambda and Omicron variants, that have or are supplanting other VOC/VOI in many countries and regions around the world.

immunology↗

bioRxiv2021

Investigating the active substance and mechanism of Jing-Fu-Kang granules via mass spectrometry technology and network pharmacology method

Jing-Fu-Kang granules (JFKG) is a famous Chinese patent medicine for the treatment of cervical spondylosis around the China, whereas the active substance and mechanism are not completely investigated clearly. In the current study, a rapid separation and identification method using UPLC-QE-Orbitrap-MS was established, 97 chemical constituents from JFKG were identified, and 16 prototype components from plasma samples after administration of JFKG were observed within 16 min. The structures of typical compounds were preliminarily speculated by comparing the retention time and fragmentation pattern. Furthermore, multiple databases were used to integrate the compound targets of JFKG, and the disease targets related to cervical spondylosis. After the intersection of the two sets of targets, a protein-protein interaction (PPI) network and a TCM-component-target-pathway-disease network were established, then using the DAVID database to perform gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis on the common targets to find related pathways. Finally, a total of 531 common targets and 136 pathways were found to participate in the mechanism. Our findings will help to further confirm the mechanism of JFKG for relieving cervical spondylosis, which will improve the scientific rationality of JFKG in clinical use, and can also assist in guiding doctors.

pharmacology and toxicology↗

bioRxiv2021

Vimentin Intermediate Filaments and Filamentous Actin Form Unexpected Interpenetrating Networks That Redefine the Cell Cortex

Vimentin intermediate filaments (VIFs) and F-actin are filamentous cytoskeletal proteins generally thought to form completely independent networks that have vastly different properties and functions. Here, we show that, unexpectedly, there exist both extensive structural and functional interactions between VIFs and F-actin. We show that VIFs and F-actin form an interpenetrating network (IPN) within the cell cortex and interact synergistically at multiple length scales. This IPN structure has important functional consequences in cells: The IPN results in enhanced contractile forces in the cell. In addition, VIFs influence the diffusive behavior of actin monomers, suggesting specific associations between actin and vimentin proteins in the cytoplasm; this facilitates formation of the IPN and has downstream effects on other actin-driven processes. The results suggest that contributions of VIFs and F-actin are strongly correlated. Such interactions counter generally accepted behavior and are broadly significant given the wide range of processes currently attributed to F-actin alone.

cell biology↗

bioRxiv2021

Protection of human ACE2 transgenic Syrian hamsters from SARS CoV-2 variants by human polyclonal IgG from hyper-immunized transchromosomic bovines

Pandemic SARS CoV-2 has been undergoing rapid evolution during spread throughout the world resulting in the emergence of many Spike protein variants, some of which appear to either evade antibody neutralization, transmit more efficiently, or potentially exhibit increased virulence. This raises significant concerns regarding the long-term efficacy of protection elicited after primary infection and/or from vaccines derived from single virus Spike (S) genotypes, as well as the efficacy of anti-S monoclonal antibody based therapeutics. Here, we used fully human polyclonal human IgG (SAB-185), derived from hyperimmunization of transchromosomic bovines with DNA plasmids encoding the SARS-CoV-2 Wa-1 strain S protein or purified ectodomain of S protein, to examine the neutralizing capacity of SAB-185 in vitro and the protective efficacy of passive SAB-185 antibody (Ab) transfer in vivo. The Ab preparation was tested for neutralization against five variant SARS-CoV-2 strains: Munich (Spike D614G), UK (B.1.1.7), Brazil (P.1) and SA (B.1.3.5) variants, and a variant isolated from a chronically infected immunocompromised patient (Spike {Delta}144-146). For the in vivo studies, we used a new human ACE2 (hACE2) transgenic Syrian hamster model that exhibits lethality after SARS-Cov-2 challenge and the Munich, UK, SA and {Delta}144-146 variants. SAB-185 neutralized each of the SARS-CoV-2 strains equivalently on Vero E6 cells, however, a control convalescent human serum sample was less effective at neutralizing the SA variant. In the hamster model, prophylactic SAB-185 treatment protected the hamsters from fatal disease and minimized clinical signs of infection. These results suggest that SAB-185 may be an effective treatment for patients infected with SARS CoV-2 variants.

microbiology↗

bioRxiv2021

Antagonists targeting eEF2 kinase rescue multiple aspects of pathophysiology in Alzheimer's disease model mice

It is imperative to develop novel therapeutic strategies for Alzheimers disease (AD) and related dementia syndromes based on solid mechanistic studies. Maintenance of memory and synaptic plasticity relies on de novo protein synthesis, which is partially regulated by phosphorylation of eukaryotic elongation factor 2 (eEF2) via its kinase eEF2K. Abnormally increased eEF2 phosphorylation and impaired mRNA translation have been linked to AD. We recently reported that prenatal genetic suppression of eEF2K is able to prevent aging-related cognitive deficits in AD model mice, suggesting the therapeutic potential of targeting eEF2K/eEF2 signaling in AD. Here, we tested two structurally distinct small-molecule eEF2K inhibitors in two different lines of AD model mice after onset of cognitive impairments. Our data revealed that treatment with eEF2K inhibitors improved AD-associated synaptic plasticity impairments and cognitive dysfunction, without altering brain amyloid {beta} (A{beta}) and tau pathology. Furthermore, eEF2K inhibition alleviated AD-associated defects in dendritic spine morphology, postsynaptic density formation, protein synthesis, and dendritic polyribosome assembly. Our results may offer critical therapeutic implications for AD, and the proof-of-principle study indicates translational implication of inhibiting eEF2K for AD and related dementia syndromes. One Sentence SummaryTreatment with eEF2K inhibitors and genetic eEF2K knockout improved cognitive deficits in Alzheimers disease model mice.

neuroscience↗

bioRxiv2021

Novel insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis.

Pulmonary alveolar microlithiasis (PAM) is an autosomal recessive lung disease caused by a deficiency in the pulmonary epithelial Npt2b sodium-phosphate co-transporter that results in accumulation of phosphate and formation of hydroxyapatite microliths in the alveolar space. The single cell transcriptomic analysis of a PAM lung explant showing a robust osteoclast gene signature in alveolar monocytes and the finding that calcium phosphate microliths contain a rich protein and lipid matrix that includes bone resorbing osteoclast enzymes suggested a role for osteoclast-like cells in the defense against microliths. While investigating the mechanisms of microlith clearance, we found that Npt2b modulates pulmonary phosphate homeostasis through effects on alternative phosphate transporter activity and alveolar osteoprotegerin, and that microliths induce osteoclast formation and activity in a receptor activator of nuclear factor-{kappa}B ligand (RANKL) and dietary phosphate dependent manner. This work reveals that Npt2b and pulmonary osteoclast-like cells play key roles in pulmonary homeostasis and suggest potential new therapeutic targets for the treatment of lung disease.

molecular biology↗

bioRxiv2021

Atp13a5 Marker Reveals Pericytes of The Central Nervous System in Mice

Perivascular mural cells including vascular smooth cells (VSMCs) and pericytes are integral components of the vascular system. In the central nervous system (CNS), pericytes are also known as the guardian of the blood-brain barrier, blood-spinal cord barrier and blood-retinal barrier, and play key roles in maintaining cerebrovascular and neuronal functions. However, the functional difference between CNS and peripheral pericytes has not been resolved at the genetic and molecular levels. Hence, the generation of reliable CNS pericyte-specific models and genetic tools remains very challenging. Here, we report a new CNS pericyte marker in mice. This cation-transporting ATPase 13A5 (Atp13a5) marker is highly specific to the pericytes in brain, spinal cord and retina. We generated a transgenic model with a knock-in tdTomato reporter and Cre recombinase. The tdTomato reporter reliably labels the CNS pericytes, but not found in any other CNS cell types including closely related VSMCs, or in peripheral organs. More importantly, Atp13a5 is turned on at embryonic day E15, suggesting brain pericytes are shaped by the developing neural environment. We hope that the new tools will allow us to further explore the heterogeneity of pericytes and achieve a better understanding of CNS pericytes in health and diseases.

neuroscience↗

bioRxiv2021

Identification of the Novel Pyroptosis-Related Gene Signature in Patients with Esophageal Adenocarcinoma

Esophageal adenocarcinoma (EAC) is a highly malignant type of digestive tract cancers with a poor prognosis despite therapeutic advances. Pyroptosis is an inflammatory form of programmed cell death, whereas the role of pyroptosis in EAC remains largely unknown. Herein, we identified a pyroptosis-related five-gene signature that was significantly correlated with the survival of EAC patients in The Cancer Genome Atlas (TCGA) cohort and an independent validation dataset. In addition, a nomogram based on the five-gene signature was constructed with novel prognostic values. Moreover, the genes in the pyroptosis-related signature, CASP1, GSDMB, IL1B, PYCARD, and ZBP1, might be involved in immune response and regulation of the tumor microenvironment. Our findings indicate that the five-gene signature provides insights into the involvement of pyroptosis in EAC progression, and is promising in the risk assessment as well as prognosis for EAC patients in clinical practice.

bioinformatics↗

bioRxiv2021

Quercetin ameliorates mitochondrial dysfunction and mitigates methamphetamine-induced anxiety-like behavior

Methamphetamine (MA) abuse results in neurotoxic outcomes, including increased anxiety and depression, during both MA use and withdrawal. Although numerous studies have reported an association between MA exposure and anxiety, the underlying mechanism remains elusive. In this study, escalating dose of MA was used to establish an MA-treated mouse model presenting anxiety behavior. RNA seq was then performed to profile the gene expression patterns in the hippocampus (HIPP). Differentially expressed genes (DEGs) were identified and function enrichment analysis was conducted to explore the underlying mechanisms. Quercetin as an mitochondria protector was used in vivo and in vitro. The C57BL/6J mice were co-treated with 50 mg/kg Quercetin and escalating MA. Anxiety behavior was evaluated by utilizing the elevated plus maze and the open field test. Transmission electron microscopy and immunohistochemistry were conducted to study the pathology of MA-inducced anxiety. The effects of MA and Quercetin on astrocytes were investigated by fluorescence staining, transmission electron microscopy, flow cytometry, and oxygen consumption rate. Western blot and qPCR were performed to analyze altered protein and gene levels of HIPP in mice and astrtocytes. The results demonstrated that forteen upregulated differentially expressed genes were identified and significantly enriched in signaling pathways related to psychiatric disorders and mitochondrial function. Interestingly, we found that quercetin was able to alleviate MA-induced anxiety-like behavior by improving neuron number and mitochondria injury. Mechanistically, quercetin can mitigate aberrant mitochondrial morphology and mitochondrial dysfunction not only by decreasing the levels of total cytoplasmic reactive oxygen species (ROS), mitochondria-derived ROS (mtROS), and mitochondrial membrane potential (MMP), but also increasing the oxygen consumption rate (OCR) and mitochondrial ATP production in vitro, indicating Quercetin ameliorated MA-induced anxiety-like behavior by modifying mitochondrial morphology and function. Furthermore, quercetin reversed OPA1 and DRP1 expression in astrocytes, and mitigated astrocyte activation and the release of inflammatory factors, which can trigger neuronal apoptosis and synaptic loss. Taken together, we provided evidence showing that MA can induce anxiety-like behavior via the induction of oxidative stress and mitochondrial dysfunction. Quercetin exerted antipsychotic activity through mitochondrial modulation, suggesting its potential for further therapeutic development in MA-induced anxiety.

neuroscience↗

bioRxiv2021

LmbU directly regulates SLINC_RS02575, SLINC_RS05540 and SLINC_RS42780, which are located outside the lmb cluster and inhibit lincomycin biosynthesis in Streptomyces lincolnensis

The productions of antibiotics are usually regulated by cluster-situated regulators (CSRs), which can directly regulate the genes within the corresponding biosynthetic gene cluster (BGC). However, few studies have looked into the regulation of CSRs on the targets outside the BGC. Here, we screened the targets of LmbU in the whole genome of S. lincolnensis, and found 14 candidate targets, among of which, 8 targets can bind to LmbU by EMSAs. Reporter assays in vivo revealed that LmbU repressed transcription of SLINC_RS02575 and SLINC_RS05540, while activated transcription of SLINC_RS42780. In addition, disruptions of SLINC_RS02575, SLINC_RS05540 and SLINC_RS42780 promoted the production of lincomycin, and qRT-PCR showed that SLINC_RS02575, SLINC_RS05540 and SLINC_RS42780 inhibited transcription of the lmb genes, indicating that all the three regulators can negatively regulate lincomycin biosynthesis. Whats more, the homologues of LmbU and its targets SLINC_RS02575, SLINC_RS05540 and SLINC_RS42780 are widely found in actinomycetes, while the distributions of DNA-binding sites (DBS) of LmbU are diverse, indicating the regulatory mechanisms of LmbU homologues in various strains are different and complicated. IMPORTANCELincomycin is widely used in clinic treatment and animal husbandry. Our previous study firstly demonstrated that LmbU, a novel transcriptional regulator family, functions as a CSR and positively regulates lincomycin biosynthesis. Here, we revealed that LmbU may act as a pleiotropic transcriptional regulator, and directly regulates SLINC_RS02575, SLINC_RS05540 and SLINC_RS42780 which are located outside the lmb cluster and negatively regulate lincomycin biosynthesis. Interestingly, the homologues of LmbU and its targets are widely found in actinomycetes, indicating the regulatory patterns of LmbU to the targets may exist in a variety of strains. Collectively, our findings elucidated the molecular mechanism with which LmbU regulates the target genes outside the lmb culster, and draw a network diagram of LmbU regulation on lincomycin biosynthesis. This lays a solid foundation for the realization of high-yield of lincomycin in industry, and provides the theoretical basis for the functional research of LmbU family proteins.

molecular biology↗

bioRxiv2021

Distinct Brain Mechanisms for Conflict Adaptation Within and Across Conflict Types

Cognitive conflict, like other cognitive processes, shows the characteristic of adaptation, i.e., conflict effects are attenuated when immediately following a conflicting event, a phenomenon known as the conflict adaptation effect (CAE). One important aspect of CAE is its sensitivity to the intertrial coherence of conflict type, i.e., behavioral CAE occurs only if consecutive trials are of the same conflict type. Although reliably observed behaviorally, the neural mechanisms underlying such a phenomenon remains elusive. With a paradigm combining the classic Simon task and Stroop task, this fMRI study examined neural correlates of conflict adaptation both within and across conflict types. The results revealed that when the conflict type repeated (but not when it alternated), the CAE-like neural activations were observed in dorsal anterior cingulate cortex, inferior frontal gyrus, superior parietal lobe, etc. (i.e., regions within typical task-positive networks). In contrast, when the conflict type alternated (but not when it repeated), we found CAE-like neural deactivations in a range of regions including bilateral superior and medial frontal gyri, bilateral angular cortex, bilateral temporal cortices, etc. (i.e., regions within the typical task-negative network). Moreover, this CAE-like neural deactivation predicts behavior performance. Network analyses suggested that these regions (for CAE-like neural activities within and across conflict type[s] respectively) can be clustered into two antagonistic networks. This evidence suggests that our adaptation to cognitive conflicts within a conflict type and across different types may rely on these two distinct neural mechanisms.

neuroscience↗

bioRxiv2021

A connectomic study of a petascale fragment of human cerebral cortex

We acquired a rapidly preserved human surgical sample from the temporal lobe of the cerebral cortex. We stained a 1 mm3 volume with heavy metals, embedded it in resin, cut more than 5000 slices at [~]30 nm and imaged these sections using a high-speed multibeam scanning electron microscope. We used computational methods to render the three-dimensional structure containing 57,216 cells, hundreds of millions of neurites and 133.7 million synaptic connections. The 1.4 petabyte electron microscopy volume, the segmented cells, cell parts, blood vessels, myelin, inhibitory and excitatory synapses, and 104 manually proofread cells are available to peruse online. Many interesting and unusual features were evident in this dataset. Glia outnumbered neurons 2:1 and oligodendrocytes were the most common cell type in the volume. Excitatory spiny neurons comprised 69% of the neuronal population, and excitatory synapses also were in the majority (76%). The synaptic drive onto spiny neurons was biased more strongly toward excitation (70%) than was the case for inhibitory interneurons (48%). Despite incompleteness of the automated segmentation caused by split and merge errors, we could automatically generate (and then validate) connections between most of the excitatory and inhibitory neuron types both within and between layers. In studying these neurons we found that deep layer excitatory cell types can be classified into new subsets, based on structural and connectivity differences, and that chandelier interneurons not only innervate excitatory neuron initial segments as previously described, but also each others initial segments. Furthermore, among the thousands of weak connections established on each neuron, there exist rarer highly powerful axonal inputs that establish multi-synaptic contacts (up to [~]20 synapses) with target neurons. Our analysis indicates that these strong inputs are specific, and allow small numbers of axons to have an outsized role in the activity of some of their postsynaptic partners.

neuroscience↗

bioRxiv2021

Nucleocapsid mutation R203K/G204R increases the infectivity, fitness and virulence of SARS-CoV-2

In addition to the mutations on the spike protein (S), co-occurring mutations on nucleocapsid (N) protein are also emerging in SARS-CoV-2 world widely. Mutations R203K/G204R on N, carried by high transmissibility SARS-CoV-2 lineages including B.1.1.7 and P.1, has a rapid spread in the pandemic during the past year. In this study, we performed comprehensive population genomic analyses and virology experiment concerning on the evolution, causation and virology consequence of R203K/G204R mutations. The global incidence frequency (IF) of 203K/204R has rose up from nearly zero to 76% to date with a shrinking from August to November in 2020 but bounced later. Our results show that the emergence of B.1.1.7 is associated with the second growth of R203K/G204R mutants. We identified positive selection evidences that support the adaptiveness of 203K/204R variants. The R203K/G204R mutant virus was created and compared with the native virus. The virus competition experiments show that 203K/204R variants possess a replication advantage over the preceding R203/G204 variants, possibly in relation to the ribonucleocapsid (RNP) assemble during the virus replication. Moreover, the 203K/204R virus increased the infectivity in a human lung cell line and induced an enhanced damage to blood vessel of infected hamsters lungs. In consistence, we observed a positive association between the increased severity of COVID-19 and the IF of 203K/204R from in silicon analysis of global clinical and epidemic data. In combination with the informatics and virology experiment, our work suggested the contribution of 203K/204R to the increased transmission and virulence of the SARS-CoV-2. In addition to mutations on the S protein, the mutations on the N protein are also important to virus spread during the pandemic.

evolutionary biology↗

bioRxiv2021

The cortical hubs related to recovery of consciousness

Background and ObjectivesThe neural mechanism that enables the recovery of consciousness in patients with unresponsive wakefulness syndrome (UWS) remains unclear. The aim of the current study is to characterize the cortical hub regions related to the recovery of consciousness in patients with UWS. MethodsVoxel-wise degree centrality analysis was adopted to identify the cortical hubs related to the recovery of consciousness, for which a total of 27 UWS patients were used, including 13 patients who emerged from UWS (UWS-E), and 14 patients who remained in UWS (UWS-R) at least three months after the experiment performance. Furthermore, other recoverable unconscious states including three independent deep sleep datasets (n = 12, 9, 9 respectively) and three independent anesthesia datasets (n = 27, 14, 6 respectively) were adopted as validation groups. Spatial similarity of the hub characteristic with the validation groups between the UWS-E and UWS-R was compared using the dice coefficient. Finally, with the cortical regions persistently shown as hubs across UWS-E and validation states, functional connectivity analysis was further performed to explore the connectivity patterns underlying the recovery of consciousness. ResultsFour cortical hubs were identified with significantly higher degree centrality for UWS-E than UWS-R, including the anterior precuneus, left inferior parietal lobule, left inferior frontal gyrus, and left middle frontal gyrus, of which the degree centrality value also positively correlated with the patients Glasgow Outcome Scale (GOS) score. Furthermore, the anterior precuneus was found to show significantly higher similarity of hub characteristics as well as functional connectivity pattern between UWS-E and validation groups, compared with UWS-R. DiscussionThe results suggest that the recovery of consciousness may be relevant to the integrity of cortical hubs, especially the anterior precuneus. The identified cortical hub regions could serve as potential targets for noninvasive stimulation aimed at promoting the patients consciousness recovery.

neuroscience↗

bioRxiv2021

Spatially coordinated heterochromatinization of distal short tandem repeats in fragile X syndrome

Short tandem repeat (STR) instability is causally linked to pathologic transcriptional silencing in a subset of repeat expansion disorders. In fragile X syndrome (FXS), instability of a single CGG STR tract is thought to repress FMR1 via local DNA methylation. Here, we report the acquisition of more than ten Megabase-sized H3K9me3 domains in FXS, including a 5-8 Megabase block around FMR1. Distal H3K9me3 domains encompass synaptic genes with STR instability, and spatially co-localize in trans concurrently with FMR1 CGG expansion and the dissolution of TADs. CRISPR engineering of mutation-length FMR1 CGG to normal-length preserves heterochromatin, whereas cut-out to pre-mutation-length attenuates a subset of H3K9me3 domains. Overexpression of a pre-mutation-length CGG de-represses both FMR1 and distal heterochromatinized genes, indicating that long-range H3K9me3-mediated silencing is exquisitely sensitive to STR length. Together, our data uncover a genome-wide surveillance mechanism by which STR tracts spatially communicate over vast distances to heterochromatinize the pathologically unstable genome in FXS. One-Sentence SummaryHeterochromatinization of distal synaptic genes with repeat instability in fragile X is reversible by overexpression of a pre-mutation length CGG tract.

genomics↗

bioRxiv2021

PRMT5 regulates ovarian follicle development by facilitating Wt1 translation

Protein arginine methyltransferase 5 (Prmt5) is the major type II enzyme responsible for symmetric dimethylation of arginine. Here, we found PRMT5 was expressed at high level in ovarian granulosa cells of growing follicles. Inactivation of Prmt5 in granulosa cells resulted in aberrant follicle development and female infertility. In Prmt5-knockout mice, follicle development was arrested with disorganized granulosa cells in which WT1 expression was dramatically reduced and the expression of steroidogenesis-related genes was significantly increased. The premature differentiated granulosa cells were detached from oocytes and follicle structure was disrupted. Mechanism studies revealed that Wt1 expression was regulated by PRMT5 at the protein level. PRMT5 facilitated IRES-dependent translation of Wt1 mRNA by methylating HnRNPA1. Moreover, the upregulation of steroidogenic genes in Prmt5-deficient granulosa cells was repressed by Wt1 overexpression. These results demonstrate PRMT5 participates in granulosa cell lineage maintenance by inducing Wt1 expression. Our study uncovers a new role of post-translational arginine methylation in granulosa cell differentiation and follicle development.

developmental biology↗

bioRxiv2021

Catch me if you can: Least myelinated white matter develops fastest during early infancy

Development of myelin, a fatty sheath that insulates nerve fibers, is critical for brain function. Myelination during infancy has been studied with histology, but postmortem data cannot evaluate the longitudinal trajectory of white matter development. Here, we obtained longitudinal diffusion MRI and quantitative MRI measures of R1 in 0, 3 and 6 months-old human infants, and (ii) developed an automated method to identify white matter bundles and quantify their properties in each infants brain. We find that R1 increases from newborns to 6-months-olds in all bundles. R1 development is nonuniform: there is faster development in white matter that is less mature in newborns, and along inferior-to-superior as well as anterior-to-posterior spatial gradients. As R1 is linearly related to myelin fraction in white matter bundles, these findings open new avenues to elucidate typical and atypical white matter myelination in early infancy, which has important implications for early identification of neurodevelopmental disorders.

neuroscience↗