Journal ArticleJ Invest Dermatol · December 2024
UBE2N, a Lys63 ubiquitin-conjugating enzyme, plays critical roles in embryogenesis and immune system development and function. However, its roles in adult epithelial tissue homeostasis and pathogenesis are unclear. We generated conditional mouse models tha ...
Full textLink to itemCite
Journal ArticleSci Rep · October 31, 2024
Enchondromas are a common tumor in bone that can occur as multiple lesions in enchondromatosis, which is associated with deformity of the affected bone. These lesions harbor somatic mutations in IDH and driving expression of a mutant Idh1 in Col2 expressin ...
Full textLink to itemCite
Journal ArticleiScience · July 19, 2024
Intratumoral heterogeneity is common in cancer, particularly in sarcomas like undifferentiated pleomorphic sarcoma (UPS), where individual cells demonstrate a high degree of cytogenic diversity. Previous studies showed that a small subset of cells within U ...
Full textLink to itemCite
Journal ArticleCell Stem Cell · June 6, 2024
Nephron progenitor cells (NPCs) self-renew and differentiate into nephrons, the functional units of the kidney. Here, manipulation of p38 and YAP activity allowed for long-term clonal expansion of primary mouse and human NPCs and induced NPCs (iNPCs) from ...
Full textLink to itemCite
Journal ArticleDev Cell · March 11, 2024
Regeneration involves gene expression changes explained in part by context-dependent recruitment of transcriptional activators to distal enhancers. Silencers that engage repressive transcriptional complexes are less studied than enhancers and more technica ...
Full textLink to itemCite
Journal ArticleNat Struct Mol Biol · December 2023
Emerging evidence suggests that cryptic translation beyond the annotated translatome produces proteins with developmental or physiological functions. However, functions of cryptic non-canonical open reading frames (ORFs) in cancer remain largely unknown. T ...
Full textLink to itemCite
Journal ArticleGenome Med · November 10, 2023
BACKGROUND: Chronic limb-threatening ischemia (CLTI), a severe manifestation of peripheral arterial disease (PAD), is associated with a 1-year limb amputation rate of approximately 15-20% and substantial mortality. A key feature of CLTI is the compromised ...
Full textLink to itemCite
Journal ArticleNature · November 2023
Trimethylation of histone H3 lysine 9 (H3K9me3) is crucial for the regulation of gene repression and heterochromatin formation, cell-fate determination and organismal development1. H3K9me3 also provides an essential mechanism for silencing transposable ele ...
Full textLink to itemCite
Journal ArticleCurr Protoc · October 2023
Cis-regulatory elements (cREs) and their long-range interactions are crucial for spatial-temporal gene regulation. While cREs can be characterized as accessible chromatin sequences, comprehensively identifying their spatial interactions remains a challenge ...
Full textLink to itemCite
Journal ArticleJ Cell Biol · August 7, 2023
A balance between self-renewal and differentiation is critical for the regenerative capacity of tissue-resident stem cells. In skeletal muscle, successful regeneration requires the orchestrated activation, proliferation, and differentiation of muscle satel ...
Full textLink to itemCite
Journal ArticleNat Genet · August 2023
Transposable elements (TEs) are parasitic DNA sequences accounting for over half of the human genome. Tight control of the repression and activation states of TEs is critical for genome integrity, development, immunity and diseases, including cancer. Howev ...
Full textLink to itemCite
Journal ArticlebioRxiv · April 3, 2023
Chronic limb-threatening ischemia (CLTI), representing the end-stage of peripheral arterial disease (PAD), is associated with a one-year limb amputation rate of ∼15-20% and significant mortality. A key characteristic of CLTI is the failure of the innate ...
Full textLink to itemCite
Journal ArticleImmunity · January 10, 2023
Obesity-induced chronic liver inflammation is a hallmark of nonalcoholic steatohepatitis (NASH)-an aggressive form of nonalcoholic fatty liver disease. However, it remains unclear how such a low-grade, yet persistent, inflammation is sustained in the liver ...
Full textLink to itemCite
Journal ArticleDevelopment · December 1, 2022
There are fundamental differences in how neonatal and adult intestines absorb nutrients. In adults, macromolecules are broken down into simpler molecular components in the lumen of the small intestine, then absorbed. In contrast, neonates are thought to re ...
Full textLink to itemCite
Journal ArticleNature · November 2022
Acute myeloid leukaemia (AML) represents a set of heterogeneous myeloid malignancies, and hallmarks include mutations in epigenetic modifiers, transcription factors and kinases1-5. The extent to which mutations in AML drive alterations in chromatin 3D stru ...
Full textLink to itemCite
Journal ArticleSci Adv · May 27, 2022
Semaphorins were originally identified as axonal guidance molecules, but they also control processes such as vascular development and tumorigenesis. The downstream signaling cascades of Semaphorins in these biological processes remain unclear. Here, we sho ...
Full textLink to itemCite
Journal ArticleBiomaterials · May 2022
Satellite cells (SCs), the adult Pax7-expressing stem cells of skeletal muscle, are essential for muscle repair. However, in vitro investigations of SC function are challenging due to isolation-induced SC activation, loss of native quiescent state, and dif ...
Full textLink to itemCite
Journal ArticleMol Cell · March 17, 2022
The long-range interactions of cis-regulatory elements (cREs) play a central role in gene regulation. cREs can be characterized as accessible chromatin sequences. However, it remains technically challenging to comprehensively identify their spatial interac ...
Full textLink to itemCite
Journal ArticleJCI Insight · November 22, 2021
Sarcomas contain a subpopulation of tumor-propagating cells (TPCs) with enhanced tumor-initiating and self-renewal properties. However, it is unclear whether the TPC phenotype in sarcomas is stable or a dynamic cell state that can derive from non-TPCs. In ...
Full textLink to itemCite
Journal ArticleJournal of Bio-X Research · September 1, 2021
Skeletal muscle plays an essential role in generating the mechanical force necessary to support the movement of our body and daily exercise. Compared with cardiac and smooth muscle, in mammals, skeletal muscle exhibits remarkable regenerative capacity in r ...
Full textCite
Journal ArticleNAR Genom Bioinform · March 2021
CRISPR is a revolutionary genome-editing tool that has been broadly used and integrated within novel biotechnologies. A major component of existing CRISPR design tools is the search engines that find the off-targets up to a predefined number of mismatches. ...
Full textLink to itemCite
Journal ArticleNat Genet · December 2020
Trimethylated histone H3 lysine 27 (H3K27me3) regulates gene repression, cell-fate determination and differentiation. We report that a conserved bromo-adjacent homology (BAH) module of BAHCC1 (BAHCC1BAH) 'recognizes' H3K27me3 specifically and enforces sile ...
Full textLink to itemCite
Journal ArticleNat Cell Biol · January 2020
Osteoclasts are multinucleated cells of the monocyte/macrophage lineage that degrade bone. Here, we used lineage tracing studies-labelling cells expressing Cx3cr1, Csf1r or Flt3-to identify the precursors of osteoclasts in mice. We identified an erythromye ...
Full textLink to itemCite
Journal ArticleMol Cell · November 7, 2019
MYOD-directed fibroblast trans-differentiation into skeletal muscle provides a unique model to investigate how one transcription factor (TF) reconfigures the three-dimensional chromatin architecture to control gene expression, which is otherwise achieved b ...
Full textLink to itemCite
Journal ArticleNature · November 2019
Oncogenes are commonly amplified on particles of extrachromosomal DNA (ecDNA) in cancer1,2, but our understanding of the structure of ecDNA and its effect on gene regulation is limited. Here, by integrating ultrastructural imaging, long-range optical mappi ...
Full textLink to itemCite
Journal ArticleNat Genet · October 2019
A large number of putative cis-regulatory sequences have been annotated in the human genome, but the genes they control remain poorly defined. To bridge this gap, we generate maps of long-range chromatin interactions centered on 18,943 well-annotated promo ...
Full textLink to itemCite
Journal ArticleProc Natl Acad Sci U S A · September 10, 2019
Nearly two-thirds of cancer patients are treated with radiation therapy (RT), often with the intent to achieve complete and permanent tumor regression (local control). RT is the primary treatment modality used to achieve local control for many malignancies ...
Full textLink to itemCite
Journal ArticleNeuron · August 21, 2019
Analysis of endogenous protein localization, function, and dynamics is fundamental to the study of all cells, including the diversity of cell types in the brain. However, current approaches are often low throughput and resource intensive. Here, we describe ...
Full textLink to itemCite
Journal ArticleNature · May 2019
Precision oncology hinges on linking tumour genotype with molecularly targeted drugs1; however, targeting the frequently dysregulated metabolic landscape of cancer has proven to be a major challenge2. Here we show that tissue context is the major determina ...
Full textLink to itemCite
Journal ArticleNature · August 2018
Mammalian cells are surrounded by neighbouring cells and extracellular matrix (ECM), which provide cells with structural support and mechanical cues that influence diverse biological processes1. The Hippo pathway effectors YAP (also known as YAP1) and TAZ ...
Full textLink to itemCite
Journal ArticleStem Cell Res Ther · February 9, 2018
BACKGROUND: Skeletal muscle satellite cell-derived myoblasts are mainly responsible for postnatal muscle growth and injury-induced regeneration. Many intracellular signaling pathways are essential for myogenic differentiation, while a number of kinases are ...
Full textLink to itemCite
Journal ArticleNat Methods · June 2017
Millions of cis-regulatory elements are predicted to be present in the human genome, but direct evidence for their biological function is scarce. Here we report a high-throughput method, cis-regulatory element scan by tiling-deletion and sequencing (CREST- ...
Full textLink to itemCite
Journal ArticleDev Cell · May 22, 2017
During mouse embryo development, both muscle progenitor cells (MPCs) and brown adipocytes (BAs) are known to derive from the same Pax7+/Myf5+ progenitor cells. However, the underlying mechanisms for the cell fate control remain unclear. In Pax7-null MPCs f ...
Full textLink to itemCite
Journal ArticleCell Rep · August 23, 2016
Recent studies have shown that STAT3 negatively regulates the proliferation of muscle satellite cells (MuSCs) and injury-induced muscle regeneration. These studies have been largely based on STAT3 inhibitors, which may produce off-target effects and are no ...
Full textLink to itemCite
Journal ArticleGenome Res · March 2016
With <2% of the human genome coding for proteins, a major challenge is to interpret the function of the noncoding DNA. Millions of regulatory sequences have been predicted in the human genome through analysis of DNA methylation, chromatin modification, hyp ...
Full textLink to itemCite
Journal ArticleFront Aging Neurosci · 2016
Alzheimer's disease (AD) is an age-related irreversible neurodegenerative disorder characterized by extracellular β Amyloid(Aβ) deposition, intracellular neurofibrillary tangles and neuronal loss. The dysfunction of neurogenesis and increased degeneration ...
Full textLink to itemCite
Journal ArticleAnn Hematol · September 2015
Acute graft-versus-host disease (aGVHD) is one of the major causes of morbidity and mortality in patients receiving allogeneic hematopoietic cell transplantation (allo-HSCT). MicroRNAs (miRs) were found to have the potential to be the new biomarkers of aGV ...
Full textLink to itemCite
Journal ArticleNature · February 19, 2015
Higher-order chromatin structure is emerging as an important regulator of gene expression. Although dynamic chromatin structures have been identified in the genome, the full scope of chromatin dynamics during mammalian development and lineage specification ...
Full textLink to itemCite
Journal ArticleFront Aging Neurosci · 2015
Alzheimer's disease (AD) is the most common cause of dementia. Amyloid β (Abeta, Aβ) deposition and intracellular tangles are the pathological hallmarks of AD. MicroRNAs (miRNAs) are small non-coding RNAs, which have been found to play very important roles ...
Full textLink to itemCite
Journal ArticleJ Biol Chem · January 3, 2014
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma found in children and young adults. It is characterized by the expression of a number of skeletal muscle-specific proteins, including MyoD and muscle α-actin. However, unlike normal myoblasts, R ...
Full textLink to itemCite
Journal ArticlePLoS One · 2014
Alzheimer's disease (AD) is the most common cause of dementia. One of the pathological hallmarks of AD is amyloid β (Aβ) deposition. MicroRNAs (miRNAs) are small non-coding RNAs whose expression levels change significantly during neuronal pathogenesis and ...
Full textLink to itemCite
Journal ArticleCell Stem Cell · August 3, 2012
In mouse skeletal muscles, Pax7 uniquely marks muscle satellite cells and plays some important yet unknown functions at the perinatal stage. To elucidate its in vivo functions, we initiated a yeast two-hybrid screening to look for Pax7-interacting proteins ...
Full textLink to itemCite
Journal ArticleProc Natl Acad Sci U S A · December 7, 2010
Mitogen-activated protein kinase kinase 6 (MKK6) is a member of the mitogen-activated protein kinase (MAPK) kinase (MAP2K) subfamily that specifically phosphorylates and activates the p38 MAPKs. Based on both biochemical and cellular assays, we found that ...
Full textLink to itemCite
Journal ArticleMol Cell Biol · September 2009
We recently showed that a leukemia inhibitory factor (LIF)-engaged signaling pathway consisting of JAK1, STAT1, and STAT3 plays dual roles in myogenic differentiation: while it participates in myoblast proliferation, it also actively represses differentiat ...
Full textLink to itemCite