Biology subjects

Zhao, Q.

Publications and source records attributed to Zhao, Q..

At least 217 records · Page 12Linked to original sources

bioRxiv2021

Oxidative phosphorylation safeguards pluripotency via UDP-N-acetylglucosamine

The roles of mitochondrial respiration in pluripotency remain largely unknown. We show here that mouse ESC mitochondria possess superior respiration capacity compared to somatic cell mitochondria, and oxidative phosphorylation (OXPHOS) generates the majority of cellular ATP in ESCs. Inhibition of OXPHOS results in extensive pluripotency and metabolic gene expression reprogram, leading to disruption of self-renewal and pluripotency. Metabolomics profiling identifies UDP-N-acetylglucosamine (UDP-GlcNAc) as one of the most significantly decreased metabolites in response to OXPHOS inhibition. The loss of ESC identity induced by OXPHOS inhibition can be ameliorated by directly adding GlcNAc both in vitro and in vivo. This work demonstrates that mitochondrial respiration, but not glycolysis, produces the majority of ATP in ESCs, and uncovers a novel mechanism whereby mitochondrial respiration is coupled with the hexosamine biosynthesis pathway to generate UDP-GlcNAc for ESC identity maintenance. SIGNIFICANCEOxidative phosphorylation (OXPHOS) and glycolysis are the two major pathways for generating ATP in mammalian cells. It is widely assumed that somatic cells utilize OXPHOS, whereas embryonic stem cells (ESCs) utilize glycolysis with low mitochondrial respiration rates even under aerobic conditions. However, the relative contribution of OXPHOS and glycolysis to ATP generation in ESCs, and the role of mitochondrial respiration in regulating ESC identity, have remained unclear. In this study, Cao et al demonstrate that mouse ESC mitochondria have a significantly higher respiration capacity than somatic cell mitochondria. Oxidative phosphorylation produces the majority of cellular ATP in mESCs and is coupled with the hexosamine biosynthesis pathway to generate UDP-GlcNAc for pluripotency maintenance. These findings define the function and mechanism of OXPHOS in regulating pluripotency, and challenge the traditional concept that mESCs rely on glycolysis over OXPHOS for their major supply of energy. HIGHLIGHTSO_LIESC mitochondria have a significantly higher respiration capability than somatic cell mitochondria C_LIO_LIOXPHOS, but not glycolysis, produces the majority of cellular ATP in ESCs C_LIO_LIOXPHOS inhibition induces a decrease in O-GlcNAcylation and the expression of pluripotency genes in blastocysts that can be partially rescued by adding GlcNAc C_LIO_LIOXPHOS is coupled with the hexosamine biosynthesis pathway for UDP-GlcNAc biosynthesis to maintain ESC identity C_LI

cell biology↗

bioRxiv2021

Large-scale field phenotyping using backpack LiDAR and GUI-based CropQuant-3D to measure structural responses to different nitrogen treatments in wheat

Plant phenomics is widely recognised as a key area to bridge the gap between traits of agricultural importance and genomic information. A wide range of field-based phenotyping solutions have been developed, from aerial-based to ground-based fixed gantry platforms and handheld devices. Nevertheless, several disadvantages of these current systems have been identified by the research community concerning mobility, affordability, throughput, accuracy, scalability, as well as the ability to analyse big data collected. Here, we present a novel phenotyping solution that combines a commercial backpack LiDAR device and our graphical user interface (GUI) based software called CropQuant-3D, which has been applied to phenotyping of wheat and associated 3D trait analysis. To our knowledge, this is the first use of backpack LiDAR for field-based plant research, which can acquire millions of 3D points to represent spatial features of crops. A key feature of the innovation is the GUI software that can extract plot-based traits from large, complex point clouds with limited computing time and power. We describe how we combined backpack LiDAR and CropQuant-3D to accurately quantify crop height and complex 3D traits such as variation in canopy structure, which was not possible to measure through other approaches. Also, we demonstrate the methodological advance and biological relevance of our work in a case study that examines the response of wheat varieties to three different levels of nitrogen fertilisation in field experiments. The results indicate that the combined solution can differentiate significant genotype and treatment effects on key morphological traits, with strong correlations with conventional manual measurements. Hence, we believe that the combined solution presented here could consistently quantify key traits at a larger scale and more quickly than heretofore possible, indicating the system could be used as a reliable research tool in large-scale and multi-location field phenotyping for crop research and breeding activities. We exhibit the systems capability in addressing challenges in mobility, throughput, and scalability, contributing to the resolution of the phenotyping bottleneck. Furthermore, with the fast maturity of LiDAR technologies, technical advances in image analysis, and open software solutions, it is likely that the solution presented here has the potential for further development in accuracy and affordability, helping us fully exploit available genomic resources.

bioinformatics↗

bioRxiv2021

Structures of the human cholecystokinin receptors in complex with agonists and antagonists

Cholecystokinin receptors, CCKAR and CCKBR, are important neuro-intestinal peptide hormone receptors and play a vital role in food intake and appetite regulation. Here we report three crystal structures of the human CCKAR in complex with different ligands, including one peptide agonist and two small-molecule antagonists, as well as two cryo-electron microscopy structures of CCKBR-gastrin in complex with Gi2 and Gq, respectively. These structures reveal the recognition pattern of different ligand types and the molecular basis of peptide selectivity in the cholecystokinin receptor family. By comparing receptor structures in different conformational states, a stepwise activation process of cholecystokinin receptors is proposed. Combined with pharmacological data, our results provide atomic details for differential ligand recognition and receptor activation mechanisms. These insights will facilitate the discovery of potential therapeutics targeting cholecystokinin receptors.

biophysics↗

bioRxiv2021

Structural basis for ligand recognition and G protein-coupling promiscuity of the cholecystokinin A receptor

Cholecystokinin A receptor (CCKAR) belongs to family A G protein-coupled receptors (GPCRs) and regulates nutrient homeostasis upon stimulation by cholecystokinin (CCK). It is an attractive drug target for gastrointestinal and metabolic diseases. One distinguishing feature of CCKAR is its ability to interact with sulfated ligand and to couple with divergent G protein subtypes, including Gs, Gi, and Gq. However, the basis for G protein coupling promiscuity and ligand recognition by CCKAR remain unknown. Here we present three cryo-electron microscopy (cryo-EM) structures of sulfated CCK-8 activated CCKAR in complex with Gs, Gi, and Gq heterotrimers, respectively. In these three structures, CCKAR presents a similar conformation, whereas conformational differences in "wavy hook" of G subunits and ICL3 of the receptor serve as determinants in G protein coupling selectivity. These structures together with mutagenesis data provide the framework for understanding the G protein coupling promiscuity by CCKAR and uncover the mechanism of receptor recognition by sulfated CCK-8.

biophysics↗

bioRxiv2021

An Enhanced Sampling Approach to the Induced Fit Docking Problem in Protein-Ligand Binding: the case of mono-ADP-ribosylation hydrolases inhibitors

A variety of enhanced sampling methods can predict free energy landscapes associated with protein/ligand binding events, characterizing in a precise way the intermolecular interactions involved. Unfortunately, these approaches are challenged by not uncommon induced fit mecchanisms. Here, we present a variant of the recently reported volume-based metadynamics (MetaD) method which describes ligand binding even when it affects protein structure. The validity of the approach is established by applying it to a substrate/enzyme complexes of pharmacological relevance: this is the mono-ADP-ribose (ADPr) in complex with mono-ADP-ribosylation hydrolases (MacroD1 and MacroD2), where induced-fit phenomena are known to be operative. The calculated binding free energies are consistent with experiments, with an absolute error less than 0.5 kcal/mol. Our simulations reveal that in all circumstances the active loops, delimiting the boundaries of the binding site, rearrange from an open to a closed conformation upon ligand binding. The calculations further provide, for the first time, the molecular basis of the experimentally observed affinity changes in ADPr binding on passing from MacroD1 to MacroD2 and all its mutants. Our study paves the way to investigate in a completely general manner ligand binding to proteins and receptors.

biochemistry↗

bioRxiv2021

Adolescent Binge Drinking is Associated with Accelerated Decline of Gray Matter Volume

The age- and time-dependent effects of binge-drinking on adolescent brain development have not been well characterized even though binge drinking is a health crisis among adolescents. The impact of binge drinking on gray matter volume development was examined using longitudinal data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA). Non-binge drinkers (n=177) were matched to binge drinkers (n=164) on potential confounders. Number of binge drinking episodes in the past year was linked to decreased volumes for total gray matter, frontal, parietal, temporal, and occipital lobes (ps<.001). Interactions of binge drinking episodes and age demonstrated stronger effects in younger subjects for total gray matter, frontal, temporal, and occipital lobes (ps<.001). Subsequent models included binge drinking coded in multiple ways. Models sensitive to number of episodes and temporal proximity to outcomes provided the best fits. Declines in gray matter volume association with binge drinking are potentially related to changes in cognition frequently reported among binge drinking adolescents. Results underscore the potential importance of delaying initiation of binge drinking and provide evidence for a dose-response relationship of binge drinking to gray matter decline. Temporally proximal binge drinking was associated more strongly with gray matter decline, suggesting the potential for recovery.

neuroscience↗

bioRxiv2021

Handcuffing intrinsically disordered regions in Mlh1-Pms1 disrupts mismatch repair

The DNA mismatch repair (MMR) factor Mlh1-Pms1 contains long intrinsically disordered regions (IDRs). While essential for MMR, their exact functions remain elusive. We performed cross-linking mass spectrometry to identify the major interactions within the Mlh1-Pms1 heterodimer and used this information to insert FRB and FKBP dimerization domains into the IDRs of Mlh1 and Pms1. Yeast bearing these constructs were grown with rapamycin to induce dimerization. Strains containing FRB and FKBP domains in the Mlh1 IDR displayed complete MMR defects when grown with rapamycin, but removing rapamycin restored MMR functions. Furthermore, linking the Mlh1 and Pms1 IDRs through FRB-FKBP dimerization disrupted Mlh1-Pms1 binding to DNA, inappropriately activated Mlh1-Pms1, and caused MMR defects in vivo. We conclude that dynamic and coordinated rearrangements of the MLH IDRs regulate how the complex clamps DNA to catalyze MMR. The application of the FRB-FKBP dimerization system to interrogate in vivo functions of a critical repair complex will be useful for probing IDRs in diverse enzymes and to probe transient loss of MMR on demand.

genetics↗

bioRxiv2021

Development of a chemiluminescence immunoassay to accurately detect African swine fever virus antibodies in serum

The outbreak of African swine fever (ASF) has caused significant economic losses to animal husbandry worldwide. Currently, there is no effective vaccine or treatment available to control the disease, and therefore, efficient disease control is dependent on early detection and diagnosis of ASF virus (ASFV). In this study, a chemiluminescent immunoassay (CLIA) was developed using the ASFV protein p54 as a serum diagnostic antigen and an anti-p54 monoclonal antibody. After optimizing the working parameters of the CLIA, the sensitivity of the established CLIA was 1:128, ASFV-specific serum antibody was identified, and there was no cross-reaction with other swine virus antibodies. After testing 49 clinical serum samples, the consistency rate between the CLIA and the World Organization for Animal Health (OIE) recommended commercial kit was 100%. Thus, this CLIA had a high degree of specificity, sensitivity, and reliability, and could be used as a rapid detection method for epidemiological investigations of ASFV infection.

microbiology↗

bioRxiv2021

Cryo-EM study on the homo-oligomeric ring formation of yeast TRiC/CCT subunits reveals TRiC ring assembly mechanism

The complex eukaryotic chaperonin TRiC/CCT helps maintain cellular protein homeostasis, however, its assembly mechanism remains largely unknown. To address the subunit specificity in TRiC assembly, we express each of the individual yeast TRiC subunit in E. coli. Our cryo-EM structural study and biochemical analyses demonstrate that CCT1/2/6 can form TRiC-like homo-oligomeric double ring (HR) complex, however ATP-hydrolysis cannot trigger their ring closure; after deletion of the long N-terminal extension, CCT5 can form the closed double-ring structure; while CCT3/4/7/8 cannot form the HRs. It appears that CCT1 forms a HR in a unique spiral configuration, and ATP-hydrolysis can drive it to re-assemble with an inserted extra subunit-pair. Our data suggest that CCT5 could be the leading subunit in ATP-hydrolysis-driven TRiC ring closure. Moreover, we demonstrate that ADP is sufficient to trigger the assembly of the HRs and TRiC from the assembly intermediate micro-complex form. Our study reveals that through evolution, the more ancestral subunits may have evolved to take more responsibilities in TRiC ring assembly, and we propose a possible assembly mechanism of TRiC involving subunit-pair insertion. Collectively, our study gives hints on the structural basis of subunit specificity in TRiC assembly and cooperativity, beneficial for future TRiC-related therapeutic strategy development.

biochemistry↗

bioRxiv2021

Deep Learning-Based Approaches for Decoding Motor Intent from Peripheral Nerve Signals

The ultimate goal of an upper-limb neuroprosthesis is to achieve dexterous and intuitive control of individual fingers. Previous literature shows that deep learning (DL) is an effective tool to decode the motor intent from neural signals obtained from different parts of the nervous system. However, it still requires complicated deep neural networks that are inefficient and not feasible to work in real-time. Here we investigate different approaches to enhance the efficiency of the DL-based motor decoding paradigm. First, a comprehensive collection of feature extraction techniques is applied to reduce the input data dimensionality. Next, we investigate two different strategies for deploying DL models: a one-step (1S) approach when big input data are available and a two-step (2S) when input data are limited. With the 1S approach, a single regression stage predicts the trajectories of all fingers. With the 2S approach, a classification stage identifies the fingers in motion, followed by a regression stage that predicts those active digits trajectories. The addition of feature extraction substantially lowers the motor decoders complexity, making it feasible for translation to a real-time paradigm. The 1S approach using a recurrent neural network (RNN) generally gives better prediction results than all the ML algorithms with mean squared error (MSE) ranges from 10-3 to 10-4 for all finger while variance accounted for (VAF) scores are above 0.8 for the most degree of freedom (DOF). This result reaffirms that DL is more advantageous than classic ML methods for handling a large dataset. However, when training on a smaller input data set as in the 2S approach, ML techniques offers a simpler implementation while ensuring comparably good decoding outcome to the DL ones. In the classification step, either machine-learning (ML) or DL models achieve the accuracy and F1 score of 0.99. Thanks to the classification step, in the regression step, both types of models result in comparable MSE and VAF scores as those of the 1S approach. Our study outlines the trade-offs to inform the implementation of real-time, low-latency, and high accuracy DL-based motor decoder for clinical applications.

bioengineering↗

bioRxiv2021

How the replication and transcription complex of SARS-CoV-2 functions in leader-to-body fusion

BackgroundCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although unprecedented efforts are underway to develop therapeutic strategies against this disease, scientists have acquired only a little knowledge regarding the structures and functions of the CoV replication and transcription complex (RTC) and 16 non-structural proteins, named NSP1-16. ResultsIn the present study, we proposed a two-route model to answer how the RTC functions in the jumping transcription of CoVs. The key step leading to this model was that the motif AAACH for METTL3 recognition flanking the transcription regulatory sequence (TRS) motif was discovered to determine the m6A methylation of SARS-CoV-2 RNAs, by reanalyzing public Nanopore RNA-seq data. As the most important finding, TRS hairpins were reported for the first time to interpret NSP15 cleavage, RNA methylation of CoVs and their association at the molecular level. In addition, we reported canonical TRS motifs of all CoVs to prove the importance of our findings. ConclusionsThe main conclusions are: (1) TRS hairpins can be used to identify recombination regions in CoV genomes; (2) RNA methylation of CoVs participates in the determination of the RNA secondary structures by affecting the formation of base pairing; and (3) The eventual determination of the CoV RTC global structure needs to consider METTL3 in the experimental design. Our findings enrich fundamental knowledge in the field of gene expression and its regulation, providing a crucial basis for future studies.

bioinformatics↗

bioRxiv2021

Mitochondrial Fission Regulates Transcription of Ribosomal Protein Genes in Embryonic Hearts

Mitochondrial dysfunction causes severe congenital heart diseases and prenatal/neonatal lethality. The lack of sufficient knowledge regarding how mitochondrial abnormalities affect cardiogenesis poses a major barrier for the development of clinical applications that target inborn heart defects due to mitochondrial deficiency. Mitochondrial morphology, which is regulated by fission and fusion, plays key roles in determining mitochondrial activity. Drp1 encodes a dynamin-related GTPase required for mitochondrial fission. To investigate the role of mitochondrial fission on cardiogenesis during the embryonic metabolic shift period, we specifically inactivated Drp1 in second heart field derived structures. Deletion of Drp1 in embryonic cardiomyocytes led to severe defects in mitochondrial morphology, ultrastructure, and activity. These defects caused increased cell death, decreased cell survival, disorganized cardiomyocytes, and embryonic lethality. Through characterizing this model, we reveal a novel AMPK-SIRT7-GABPB axis that relays the mitochondrial fission anomaly to reduced transcription of ribosomal protein genes in mutant cardiomyocytes. We therefore provide the first mouse genetic evidence to show that mitochondrial fission is essential for embryonic heart development. Furthermore, we uncovered a novel signaling cascade that mediates the crosstalk between mitochondrial dysfunction and protein synthesis. Our research provides further mechanistic insight regarding how mitochondrial dysfunction causes pathological molecular and cellular alterations during cardiogenesis.

developmental biology↗

bioRxiv2021

A Facile and Rapid Route to Self-Digitization of Samples into a High Density Microwell Array for Digital Bioassays

Digital bioassays are powerful methods to detect rare analytes from complex mixtures and study the temporal processes of individual entities within biological systems. In digital bioassays, a crucial first step is the discretization of samples into a large number of identical independent partitions. Here, we developed a rapid and facile sample partitioning method for versatile digital bioassays. This method is based on a detachable self-digitization (DSD) chip which couples a reversible assembly configuration and a predegassing-based self-pumping mechanism to achieve an easy, fast and large-scale sample partitioning. The DSD chip consists of a channel layer used for loading sample and a microwell layer used for holding the sample partitions. Benefitting from its detachability, the chip avoids a lengthy oil flushing process used to remove the excess sample in loading channels and can compartmentalize a sample into more than 100,000 wells of picoliter volume with densities up to 14,000 wells/cm2 in less than 30 s. We also demonstrated the utility of the proposed method by applying it to digital PCR and digital microbial assays.

bioengineering↗

bioRxiv2021

The PELOTA-HBS1 Complex Orchestrates mRNA Translation Surveillance and PDK1-mediated Plant Growth and Development

The quality control system for messenger RNA is fundamental for cellular activities in eukaryotes. To elucidate the molecular mechanism of 3-Phosphoinositide-Dependent Protein Kinase1 (PDK1), an essential regulator throughout growth and development of eukaryotes, a forward genetic approach was employed to screen for suppressors of the loss-of-function T-DNA insertional pdk1.1 pdk1.2 double mutant in Arabidopsis. Notably, the severe growth attenuation of pdk1.1 pdk1.2 is rescued by sop21 (suppressor of pdk1.1 pdk1.2) that harbours a loss-of-function mutation in PELOTA1 (PEL1). PEL1 is a homologue of mammalian PELOTA and yeast DOM34, which form a heterodimeric complex with the GTPase HBS1, responsible for ribosome rescue to assure the quality and fidelity of mRNA molecules. Genetic analysis further reveals that the dysfunction of PEL1-HBS complex fails to degrade the T-DNA-disrupted, truncated but functional PDK1 transcripts, thus rescuing pdk1.1 pdk1.2. Our studies demonstrate the functionality and identify the essential functions of a homologous PELOTA-HBS1 complex in higher plant, and provide novel insights into the mRNA quality control mechanism.

plant biology↗

bioRxiv2020

Using Genetic Information to Improve the Prediction of Individual Food Choice: A Case Study of Alcoholic Beverages

Individual food choices and consumption are closely relating to ones diet, nutrition, and health. Using the case of alcoholic beverages, this study extends the random-utility framework by incorporating genetic information into consumer demand models, and demonstrates the significant impact of genetic factors on individual food choice decisions in a novel way. Integrating individual-level responses of discrete choice experiments (DCE), genotyping data, and socioeconomic/demographic characteristics of 484 participants collected from face-to-face interviews in mainland China, we employ a machine learning-based classification (MLC) approach to identify and predict individual choices. We show that genetic factors are critical to explaining variations in both general drinking behavior and choices of particular products. We systematically compared the performance of traditional discrete choice models and MLC models without and with genetic factors. The MLC predictive model with both socio-demographic and genetic features yields the highest accuracy of 74.7% and AUC-ROC of 0.85. Our findings warrant further economic studies of human behaviors with the integration of genetic data.

genetics↗

bioRxiv2020

Sterilizing immunity against SARS-CoV-2 in hamsters conferred by a novel recombinant subunit vaccine

A safe and effective SARS-CoV-2 vaccine is essential to avert the on-going COVID-19 pandemic. Here, we developed a subunit vaccine, which is comprised of CHO-expressed spike ectodomain protein (StriFK) and nitrogen bisphosphonates-modified zinc-aluminum hybrid adjuvant (FH002C). This vaccine candidate rapidly elicited the robust humoral response, Th1/Th2 balanced helper CD4 T cell and CD8 T cell immune response in animal models. In mice, hamsters, and non-human primates, 2-shot and 3-shot immunization of StriFK-FH002C generated 28- to 38-fold and 47- to 269-fold higher neutralizing antibody titers than the human COVID-19 convalescent plasmas, respectively. More importantly, the StriFK-FH002C immunization conferred sterilizing immunity to prevent SARS-CoV-2 infection and transmission, which also protected animals from virus-induced weight loss, COVID-19-like symptoms, and pneumonia in hamsters. Vaccine-induced neutralizing and cell-based receptor-blocking antibody titers correlated well with protective efficacy in hamsters, suggesting vaccine-elicited protection is immune-associated. The StriFK-FH002C provided a promising SARS-CoV-2 vaccine candidate for further clinical evaluation.

microbiology↗

bioRxiv2020

Methylation of Dual Specificity Phosphatase 4 Controls Cell Differentiation

A collection of signaling and epigenetic events needs to be orchestrated for normal development of hematopoietic lineages. While mitogen-activated protein (MAP) kinases (MAPKs) and multiple epigenetic modulators have been implicated in the megakaryocytic (Mk) cell differentiation, the underlying molecular mechanisms of signaling-epigenetic crosstalk remain unclear. MAPKs are in general inactivated by dual specificity phosphatases (DUSPs), whose activities are tightly regulated by various posttranslational modifications. Using knockdown screening and single-cell transcriptional analysis, we determined that DUSP4 is the phosphatase that inactivates p38 MAPK in hematopoietic cells and serves as a key regulator to promote Mk differentiation. With the nextgeneration Bioorthogonal Profiling of Protein Methylation technology for live cells, we identified DUSP4 as a PRMT1 substrate. Mechanistically, PRMT1-mediated Arg351 methylation of DUSP4 triggers its ubiquitinylation by HUWE1 (an E3 ligase) and then degradation, which results in p38 MAPK activation and inhibition of Mk differentiation in vitro and in vivo. Interestingly, the mechanistic axis of the DUSP4 degradation and p38 activation is also associated with a transcriptional signature of immune activation and thus argues immunological roles of Mk cells. Collectively, these results demonstrate a critical role of PRMT1-mediated posttranslational modification of DUSP4 in regulation of Mk differentiation and maturation. In the context of thrombocytopenia observed in myelodysplastic syndromes (MDS), we demonstrated that high levels of p38 MAPK and PRMT1 are associated with low platelet counts and adverse prognosis, while pharmacological inhibition of p38 MAPK or PRMT1 stimulates megakaryopoiesis in MDS samples. These findings provide novel mechanistic insights into the role of the PRMT1-DUSP4-p38 axis on Mk differentiation and present a targeting strategy for treatment of thrombocytopenia associated with myeloid malignancies such as MDS.

cell biology↗

bioRxiv2020

A secreted endoribonuclease ENDU-2 from the soma protects germline immortality in C. elegans

Multicellular organisms coordinate tissue specific response to environmental information via both cell-autonomous and non-autonomous mechanisms. In addition to secreted ligands, secreted small RNAs have recently been reported to regulate gene expression across tissue boundaries. Here we show that the conserved poly-U specific endoribonuclease ENDU-2 is secreted from the soma and taken-up by the germline to ensure germline immortality at elevated temperature in C. elegans. ENDU-2 binds to mature mRNAs and negatively regulates mRNA abundance both in the soma and the germline. While ENDU-2 promotes RNA decay in the soma directly via its endoribonuclease activity, ENDU-2 prevents misexpression of soma-specific genes in the germline and preserves germline immortality independent of its RNA-cleavage activity. In summary, our results suggest that the secreted RNase ENDU-2 transmits environmental information across tissue boundaries and contributes to maintenance of stem cell immortality probably via retaining a stem cell specific program of gene expression.

molecular biology↗