A5086728591- Genomics and Chromatin Dynamics
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Cancer Cells and Metastasis
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Peroxisome Proliferator-Activated Receptors
- Cancer-related molecular mechanisms research
- Adipose Tissue and Metabolism
- RNA modifications and cancer
- Brain Metastases and Treatment
- Chemical Reactions and Isotopes
- Diet and metabolism studies
- Axon Guidance and Neuronal Signaling
- Mechanisms of cancer metastasis
- Genetics and Neurodevelopmental Disorders
- Developmental Biology and Gene Regulation
- Kruppel-like factors research
- Neurogenesis and neuroplasticity mechanisms
- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Renal and related cancers
- Hearing, Cochlea, Tinnitus, Genetics
- Prostate Cancer Treatment and Research
- Animal Genetics and Reproduction
Nankai University
2020-2024
The First Affiliated Hospital, Sun Yat-sen University
2023-2024
Sun Yat-sen University
2023-2024
Broad Center
2011-2020
University of Southern California
2011-2020
State Key Laboratory of Medicinal Chemical Biology
2020
University of Coimbra
2019
Shandong University
2018
Western University
2018
Institute for Stem Cell Biology and Regenerative Medicine
2016
Recent evidence suggests that many endogenous circular RNAs (circRNAs) may play roles in biological processes. However, the expression patterns and functions of circRNAs human diseases are not well understood. Computationally identifying from total RNA-seq data is a primary step studying their pattern roles. In this work, we have developed computational pipeline named UROBORUS to detect data. By applying 46 gliomas normal brain samples, detected thousands supported by at least two read...
Transcription factor Kruppel-like 4 (Klf4) is essential for somatic cell reprogramming. In addition, Klf4 seems to play a redundant role along with other Klf family proteins in embryonic stem (ES) self-renewal. However, how regulates ES self-renewal and reprogramming still poorly understood. Here we report that required both maintenance of pluripotency the expression prevents differentiation response withdrawal leukemia inhibitory (LIF) or bone morphogenetic protein (BMP4). directly binds...
Genome-wide association studies (GWAS) have revolutionized the field of cancer genetics, but causal links between increased genetic risk and onset/progression disease processes remain to be identified. Here we report first step in such an endeavor for prostate cancer. We provide a comprehensive annotation 77 known loci, based upon highly correlated variants biologically relevant chromatin annotations— identified 727 potentially functional SNPs. also detailed account possible protein...
GABAergic interneurons are inhibitory neurons of the nervous system that play a vital role in neural circuitry and activity. They so named due to their release neurotransmitter gamma-aminobutyric acid (GABA), occupy different areas brain. This review will focus primarily on mammalian cerebral cortex from developmental standpoint. There is diverse amount cortical interneuronal subtypes may be categorized by number characteristics; this classify them largely protein markers they express. The...
Somatic cells can be reprogrammed to induced pluripotent stem (iPS) by ectopic expression of specific sets transcription factors. Oct4, Sox2, and Klf4, factors that share many target genes in embryonic (ES) cells, are critical components various reprogramming protocols. Nevertheless, it remains unclear whether these function together or separately reprogramming. Here we show Klf4 interacts directly with Oct4 Sox2 when expressed at levels sufficient induce iPS cells. Endogenous also mouse ES...
Abstract Hematogenous metastasis is initiated by a subset of circulating tumor cells (CTC) shed from primary or metastatic tumors into the blood circulation. Thus, CTCs provide unique patient biopsy resource to decipher cellular subpopulations that initiate and their molecular properties. However, one crucial question whether derived expanded ex vivo patients recapitulate human disease in an animal model. Here, we show CTC lines established with breast cancer are capable generating...
Although limited proteolysis of the histone H3 N-terminal tail (H3NT) is frequently observed during mammalian differentiation, specific genomic sites targeted for H3NT and functional significance cleavage remain largely unknown. Here we report first method to identify examine H3NT-cleaved regions in mammals, called chromatin immunoprecipitation (ChIP) acetylated (ChIPac). By applying ChIPac combined with deep sequencing (ChIPac-seq) an established cell model osteoclast discovered that...
Abstract Chromodomain helicase DNA-binding protein 8 ( CHD8 ) was identified as a leading autism spectrum disorder (ASD) candidate gene by whole-exome sequencing and subsequent targeted-sequencing studies. De novo loss-of-function mutations were in 12 individuals with ASD zero controls, accounting for highly significant association. Small interfering RNA-mediated knockdown of human neural progenitor cells followed RNA revealed that insufficiency results altered expression 1715 genes,...
Exonic deletions in NRXN1 have been associated with several neurodevelopmental disorders, including autism, schizophrenia and developmental delay. However, the molecular mechanism by which impact neurodevelopment remains unclear. Here we used human induced pluripotent stem cells (hiPSCs) embryonic (hESCs) as models to investigate functional impacts of knockdown. We first generated hiPSCs from skin fibroblasts differentiated them into neural (NSCs). reduced expression NSCs via a controlled...
DNA methyltransferases (DNMTs) play an important role in establishing and maintaining methylation. Aberrant expression of DNMTs their isoforms has been found many types cancer, contribution to aberrant methylation proposed. Here, we generated HEK 293T cells stably transfected with each 13 different (DNMT1, two DNMT3A isoforms, nine DNMT3B DNMT3L) assessed the changes induced by DNMT. We obtained profiles repetitive elements 1505 CpG sites from 808 cancer-related genes. that have specific...
Abstract Linker histone H1 is a protein component of chromatin and has been linked to higher-order compaction global gene silencing. However, growing body evidence suggests that plays gene-specific role, regulating relatively small number genes. Here we show H1.2, one the subtypes, overexpressed in cancer cells contributes H1.2 gets recruited distinct regions manner dependent on EZH2-mediated H3K27me3 inhibits transcription multiple growth suppressive genes via modulation architecture. The...
Abstract Genetic sharing is extensively observed for autoimmune diseases, but the causal variants and their underlying molecular mechanisms remain largely unknown. Through systematic investigation of disease pleiotropic loci, we found most these shared genetic effects are transmitted from regulatory code. We used an evidence-based strategy to functionally prioritize identify target genes. A top-ranked variant, rs4728142, yielded many lines evidence as being causal. Mechanistically,...
Wnt signaling has been implicated in promoting somatic cell reprogramming. However, its molecular mechanisms remain unknown. Here we report that Wnt/β-catenin enhances iPSCs induction at the early stage of The augmented reprogramming induced by β-catenin is not due to increased total population or activation c-Myc. In addition, interacts with factors Klf4, Oct4, and Sox2, further enhancing expression pluripotency circuitry genes. These studies reveal novel underlying regulation cells signaling.
The Wnt receptor Ryk is an evolutionary-conserved protein important during neuronal differentiation through several mechanisms, including γ-secretase cleavage and nuclear translocation of its intracellular domain (Ryk-ICD). Although the pathway may be neuroprotective, role in neurodegenerative disease remains unknown. We found that up-regulated neurons expressing mutant huntingtin (HTT) models Huntington's (HD). Further investigation Caenorhabditis elegans mouse striatal cell HD provided a...
Kruppel-like factor 4 (Klf4) is a zinc-finger-containing protein that plays critical role in diverse cellular physiology. While most of these functions attribute to its as transcription factor, it postulated Klf4 may play other than transcriptional regulation. Here we demonstrate loss neural progenitor cells (NPCs) leads increased neurogenesis and reduced self-renewal mice. In addition, interacts with RNA-binding Staufen1 (Stau1) RNA helicase Ddx5/17. They function together complex maintain...
Genome-wide association studies identified single-nucleotide polymorphism (SNP) rs55958994 as a significant variant associated with increased susceptibility to prostate cancer. However, the mechanisms by which this SNP mediates risk cancer are still unknown. In study, we show that is located in an enhancer active cells. Deletion of from tumor cells resulted decreased initiation, growth, and invasive migration, well loss stem-like Using combination capture chromosome conformation (Capture-C)...
Temozolomide (TMZ) is a frequently used chemotherapy for glioma; however, chemoresistance major problem limiting its effectiveness. Thus, knowledge of mechanisms underlying this outcome could improve patient prognosis. Here, we report that deletion regulatory element in the HOTAIR locus increases glioma cell sensitivity to TMZ and alters transcription multiple genes. Analysis combination RNA-seq, Capture Hi-C, survival data suggests CALCOCO1 ZC3H10 are target genes repressed by both function...
Neural progenitor cells (NPCs) are multipotent that can self-renew and differentiate into neurons glial cells. However, mechanisms control their fate decisions poorly understood. Here, we show Smek1, a regulatory subunit of the serine/threonine protein phosphatase PP4, promotes neuronal differentiation suppresses proliferative capacity NPCs. We identify cell polarity Par3, negative regulator differentiation, as Smek1 substrate demonstrate its activity. also which is predominantly nuclear in...