ABSTRACT
To comprehensively investigate the molecular transmission patterns of HIV-1 genotypes among men who have sex with men (MSM) in Chongqing, we employed 392 pol sequences of MSM to construct a phylogenetic tree and gene transmission network. Among the viral subtypes, CRF07_BC accounted for 73.2% (287/392) and CRF01_AE accounted for 20.7% (81/392), emerging as the predominant subtypes in this investigation. Additionally, we observed the presence of CRF55_01B, subtype B, CRF08_BC and other circulating recombinant forms. The HIV-1 molecular network was constructed with a gene distance threshold of 1.5%, resulting in an entry rate of 61.4% (241/392). Within the network, we identified a total of 23 molecular clusters, with the largest cluster being the CRF07_BC molecular cluster comprising 148 node values. Transmitted drug-resistance (TDR) mutations were found in 4.34% of the cases, with 1.79% associated with protease inhibitors (PIs), 0.51% with nucleoside reverse transcriptase inhibitors (NRTIs), and 2.55% with non-nucleoside reverse transcriptase inhibitors (NNRTIs). Statistical analysis indicated a higher enrollment rate in the HIV-1 molecular network among infected individuals with the CRF07_BC subtype, those identifying with same-sex sexual roles as "vers," and individuals with higher education levels. This suggests the need for strengthened investigation and intervention in this population to prevent the formation of larger transmission clusters. Furthermore, continuous monitoring of the HIV-1 molecular dynamics network is necessary to promptly and accurately track changes in molecular epidemic characteristics.
Subject(s)
Drug Resistance, Viral , HIV Infections , HIV-1 , Homosexuality, Male , Phylogeny , Humans , Male , China/epidemiology , Homosexuality, Male/statistics & numerical data , HIV-1/genetics , HIV-1/drug effects , Drug Resistance, Viral/genetics , Adult , HIV Infections/epidemiology , HIV Infections/genetics , HIV Infections/transmission , Genotype , Acquired Immunodeficiency Syndrome/epidemiology , Acquired Immunodeficiency Syndrome/transmission , Middle Aged , MutationABSTRACT
LIN28A is important in somatic reprogramming and pluripotency regulation. Although previous studies addressed that LIN28A can repress let-7 microRNA maturation in the cytoplasm, few focused on its role within the nucleus. Here, we show that the nucleolus-localized LIN28A protein undergoes liquid-liquid phase separation (LLPS) in mouse embryonic stem cells (mESCs) and in vitro. The RNA binding domains (RBD) and intrinsically disordered regions (IDR) of LIN28A contribute to LIN28A and the other nucleolar proteins' phase-separated condensate establishment. S120A, S200A and R192G mutations in the IDR result in subcellular mislocalization of LIN28A and abnormal nucleolar phase separation. Moreover, we find that the naive-to-primed pluripotency state conversion and the reprogramming are associated with dynamic nucleolar remodeling, which depends on LIN28A's phase separation capacity, because the LIN28A IDR point mutations abolish its role in regulating nucleolus and in these cell fate decision processes, and an exogenous IDR rescues it. These findings shed light on the nucleolar function in pluripotent stem cell states and on a non-canonical RNA-independent role of LIN28A in phase separation and cell fate decisions.
Subject(s)
Phase Separation , Pluripotent Stem Cells , RNA-Binding Proteins , Animals , Mice , Cell Differentiation/genetics , Cell Nucleolus/metabolism , Pluripotent Stem Cells/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolismABSTRACT
Lipids are indispensable for energy storage, membrane structure and cell signalling. However, dynamic changes in various categories of endogenous lipids in mammalian early embryonic development have not been systematically characterized. Here we comprehensively investigated the dynamic lipid landscape during mouse and human early embryo development. Lipid signatures of different developmental stages are distinct, particularly for the phospholipid classes. We highlight that the high degree of phospholipid unsaturation is a conserved feature as embryos develop to the blastocyst stage. Moreover, we show that lipid desaturases such as SCD1 are required for in vitro blastocyst development and blastocyst implantation. One of the mechanisms is through the regulation of unsaturated fatty-acid-mediated fluidity of the plasma membrane and apical proteins and the establishment of apical-basal polarity during development of the eight-cell embryo to the blastocyst. Overall, our study provides an invaluable resource about the remodelling of the endogenous lipidome in mammalian preimplantation embryo development and mechanistic insights into the regulation of embryogenesis and implantation by lipid unsaturation.