Biology subjects

Huang, G.

Publications and source records attributed to Huang, G..

112 records · Page 7Linked to original sources

bioRxiv2019

Mutant p53 Drives Clonal Hematopoiesis through Modulating Epigenetic Pathway

Clonal hematopoiesis of indeterminate potential (CHIP) increases with age and is associated with increased risks of hematological malignancies. While TP53 mutations have been identified in CHIP, the molecular mechanisms by which mutant p53 promotes hematopoietic stem and progenitor cell (HSPC) expansion are largely unknown. We discovered that mutant p53 confers a competitive advantage to HSPCs following transplantation and promotes HSPC expansion after radiation-induced stress. Mechanistically, mutant p53 interacts with EZH2 and enhances its association with the chromatin, thereby increasing the levels of H3K27me3 in genes regulating HSPC self-renewal and differentiation. Further, genetic and pharmacological inhibition of EZH2 decrease the repopulating potential of p53 mutant HSPCs. Thus, we have uncovered an epigenetic mechanism by which mutant p53 drives clonal hematopoiesis. Our work will likely establish epigenetic regulator EZH2 as a novel therapeutic target for preventing CHIP progression and treating hematological malignancies with TP53 mutations.

cancer biology↗

bioRxiv2018

Abundance and community composition of comammox bacteria in different ecosystems by a universal primer set

Complete ammonia oxidizing bacteria (CAOB) have been recognized as a new member of ammonia-oxidizing microorganisms (AOMs) due to its single-step nitrification capability. However, the abundance and diversity of CAOB in environmental ecosystems were still far from known owing to the lack of specific molecular marker. Herein, a universal primer set specifically targeting the both clades of CAOB amoA gene with high specificity and coverage was successfully designed. Intriguingly, real-time quantitative PCR tests revealed that CAOB were ubiquitous and unexpectedly abundant in agricultural soils, river sediments, intertidal zones, drinking water and wastewater treatment systems. Phylogenetic analysis indicated that clade A existed in all the five types of ecosystems, while clade B were only detected in soil and sediment samples. Four sub-clusters were further classified within clade A, in which N. nitrosa cluster dominated CAOB amoA in activated sludge samples while the new recognized soil cluster was the primary constitute in soils. Moreover, the niche specialization between different CAOB species and the environmental conditions were supposed to be the primary driven force to shape the diversity and community of CAOB. This study provided a strong evidence in support of the ubiquities and high abundances of CAOB in various environmental ecosystems and highlighted the significance of including CAOB as the new member of AOMs to re-evaluate the biogeochemical nitrogen cycle.

microbiology↗

bioRxiv2018

Amino Acids Changes and Muscle Damage During the 400 km Ultra Trail Gobi Race

Current researches demonstrated that completing the Ultra Trail Gobi (UTG) could lead to severe muscle damage. Our study was designed to analysis the muscle damage and amino acid changes reacted to a 400 km ultra-endurance race in experienced runners. Peripheral blood samples from 16 male athletes (mean age 40.3 {+/-} 7.0 years, mean finish time 121.2 {+/-} 21.8 hours), taken 48 h before and immediately after completing the Ultra Trail Gobi Race (UTG), were analyzed for 39 amino acids, 15 steroid hormones and 4 muscle damage factors. In all participants, the 4 biomarkers for muscle damage, i.e., creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) increased significantly after the race, whose mean post-race values were 13.7-, 7.3-, 4.7- and 1.5-fold higher than the pre-race values, respectively. 5 amino acids, i.e., alanine, valine, proline, ornithine and citrulline showed significant decrease, whose mean values decreased by 40.4 {+/-} 18.7%, 38.9 {+/-} 9.3%, 48.1 {+/-} 15.2%, 44.8 {+/-} 15.1% and 23.4 {+/-} 30.8% after the race, respectively. Our study revealed that progressive decline in amino acids contents may further contribute to the factors increasing the muscle damage during the UTG.

physiology↗

bioRxiv2018

Overdispersed gene expression characterizes schizophrenic brains

Schizophrenia (SCZ) is a severe, highly heterogeneous psychiatric disorder with varied clinical presentations. The polygenic genetic architecture of SCZ makes identification of causal variants daunting. Gene expression analyses have shown that SCZ may result in part from transcriptional dysregulation of a number of genes. However, most of these studies took the commonly used approach--differential gene expression analysis, assuming people with SCZ are a homogenous group, all with similar expression levels for any given gene. Here we show that the overall gene expression variability in SCZ is higher than that in an unaffected control (CTL) group. Specifically, we applied the test for equality of variances to the normalized expression data generated by the CommonMind Consortium (CMC) and identified 87 genes with significantly higher expression variances in the SCZ group than the CTL group. One of the genes with differential variability, VEGFA, encodes a vascular endothelial growth factor, supporting a vascular-ischemic etiology of SCZ. We also applied a Mahalanobis distance-based test for multivariate homogeneity of group dispersions to gene sets and identified 19 functional gene sets with higher expression variability in the SCZ group than the CTL group. Several of these gene sets are involved in brain development (e.g., development of cerebellar cortex, cerebellar Purkinje cell layer and neuromuscular junction), supporting that structural and functional changes in the cortex cause SCZ. Finally, using expression variability QTL (evQTL) analysis, we show that common genetic variants contribute to the increased expression variability in SCZ. Our results reveal that SCZ brains are characterized by overdispersed gene expression, resulting from dysregulated expression of functional gene sets pertaining to brain development, necrotic cell death, folic acid metabolism, and several other biological processes. Using SCZ as a model of complex genetic disorders with a heterogeneous etiology, our study provides a new conceptual framework for variability-centric analyses. Such a framework is likely to be important in the era of personalized medicine. (313 words)

genetics↗