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Yarui Diao

Assistant Professor of Cell Biology
Cell Biology

Selected Publications


A screen for regeneration-associated silencer regulatory elements in zebrafish.

Journal Article Dev 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 text Link to item Cite

CRISPR-Cas9-based functional interrogation of unconventional translatome reveals human cancer dependency on cryptic non-canonical open reading frames.

Journal Article Nat 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 text Link to item Cite

Skeletal muscle regeneration failure in ischemic-damaged limbs is associated with pro-inflammatory macrophages and premature differentiation of satellite cells.

Journal Article Genome 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 text Link to item Cite

TNRC18 engages H3K9me3 to mediate silencing of endogenous retrotransposons.

Journal Article Nature · 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 text Link to item Cite

HiCAR: Analysis of Open Chromatin Associated Long-range Chromatin Interaction Using Low-Input Materials.

Journal Article Curr 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 text Link to item Cite

Single-cell chromatin accessibility profiling reveals a self-renewing muscle satellite cell state.

Journal Article J 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 text Link to item Cite

Crosstalk between RNA m6A and DNA methylation regulates transposable element chromatin activation and cell fate in human pluripotent stem cells.

Journal Article Nat 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 text Link to item Cite

Pro-inflammatory macrophages impair skeletal muscle regeneration in ischemic-damaged limbs by inducing precocious differentiation of satellite cells.

Journal Article bioRxiv · 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 text Link to item Cite

Prolonged hypernutrition impairs TREM2-dependent efferocytosis to license chronic liver inflammation and NASH development.

Journal Article Immunity · 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 text Link to item Cite

Maf family transcription factors are required for nutrient uptake in the mouse neonatal gut.

Journal Article Development (Cambridge, England) · December 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 text Cite

Subtype-specific 3D genome alteration in acute myeloid leukaemia.

Journal Article Nature · 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 text Link to item Cite

The Hippo pathway mediates Semaphorin signaling.

Journal Article Sci 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 text Link to item Cite

Myoblast deactivation within engineered human skeletal muscle creates a transcriptionally heterogeneous population of quiescent satellite-like cells.

Journal Article Biomaterials · 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 text Link to item Cite

HiCAR is a robust and sensitive method to analyze open-chromatin-associated genome organization.

Journal Article Mol 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 text Link to item Cite

Tumor-propagating side population cells are a dynamic subpopulation in undifferentiated pleomorphic sarcoma.

Journal Article JCI 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 text Link to item Cite

Function and regulation of muscle stem cells in skeletal muscle development and regeneration: a narrative review

Journal Article Journal 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 text Cite

CRISPR-SE: a brute force search engine for CRISPR design.

Journal Article NAR 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 text Link to item Cite

BAHCC1 binds H3K27me3 via a conserved BAH module to mediate gene silencing and oncogenesis.

Journal Article Nat 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 text Link to item Cite

Erythromyeloid progenitors give rise to a population of osteoclasts that contribute to bone homeostasis and repair.

Journal Article Nat 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 text Link to item Cite

A screen for regeneration-associated silencer regulatory elements in zebrafish.

Journal Article Dev 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 text Link to item Cite

CRISPR-Cas9-based functional interrogation of unconventional translatome reveals human cancer dependency on cryptic non-canonical open reading frames.

Journal Article Nat 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 text Link to item Cite

Skeletal muscle regeneration failure in ischemic-damaged limbs is associated with pro-inflammatory macrophages and premature differentiation of satellite cells.

Journal Article Genome 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 text Link to item Cite

TNRC18 engages H3K9me3 to mediate silencing of endogenous retrotransposons.

Journal Article Nature · 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 text Link to item Cite

HiCAR: Analysis of Open Chromatin Associated Long-range Chromatin Interaction Using Low-Input Materials.

Journal Article Curr 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 text Link to item Cite

Single-cell chromatin accessibility profiling reveals a self-renewing muscle satellite cell state.

Journal Article J 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 text Link to item Cite

Crosstalk between RNA m6A and DNA methylation regulates transposable element chromatin activation and cell fate in human pluripotent stem cells.

Journal Article Nat 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 text Link to item Cite

Pro-inflammatory macrophages impair skeletal muscle regeneration in ischemic-damaged limbs by inducing precocious differentiation of satellite cells.

Journal Article bioRxiv · 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 text Link to item Cite

Prolonged hypernutrition impairs TREM2-dependent efferocytosis to license chronic liver inflammation and NASH development.

Journal Article Immunity · 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 text Link to item Cite

Maf family transcription factors are required for nutrient uptake in the mouse neonatal gut.

Journal Article Development (Cambridge, England) · December 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 text Cite

Subtype-specific 3D genome alteration in acute myeloid leukaemia.

Journal Article Nature · 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 text Link to item Cite

The Hippo pathway mediates Semaphorin signaling.

Journal Article Sci 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 text Link to item Cite

Myoblast deactivation within engineered human skeletal muscle creates a transcriptionally heterogeneous population of quiescent satellite-like cells.

Journal Article Biomaterials · 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 text Link to item Cite

HiCAR is a robust and sensitive method to analyze open-chromatin-associated genome organization.

Journal Article Mol 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 text Link to item Cite

Tumor-propagating side population cells are a dynamic subpopulation in undifferentiated pleomorphic sarcoma.

Journal Article JCI 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 text Link to item Cite

Function and regulation of muscle stem cells in skeletal muscle development and regeneration: a narrative review

Journal Article Journal 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 text Cite

CRISPR-SE: a brute force search engine for CRISPR design.

Journal Article NAR 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 text Link to item Cite

BAHCC1 binds H3K27me3 via a conserved BAH module to mediate gene silencing and oncogenesis.

Journal Article Nat 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 text Link to item Cite

Erythromyeloid progenitors give rise to a population of osteoclasts that contribute to bone homeostasis and repair.

Journal Article Nat 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 text Link to item Cite

Transcription Factor-Directed Re-wiring of Chromatin Architecture for Somatic Cell Nuclear Reprogramming toward trans-Differentiation.

Journal Article Mol 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 text Link to item Cite

Circular ecDNA promotes accessible chromatin and high oncogene expression.

Journal Article Nature · 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 text Link to item Cite

A compendium of promoter-centered long-range chromatin interactions in the human genome.

Journal Article Nat 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 text Link to item Cite

Neutrophils promote tumor resistance to radiation therapy.

Journal Article Proc 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 text Link to item Cite

Plug-and-Play Protein Modification Using Homology-Independent Universal Genome Engineering.

Journal Article Neuron · 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 text Link to item Cite

NAD metabolic dependency in cancer is shaped by gene amplification and enhancer remodelling.

Journal Article Nature · 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 text Link to item Cite

RAP2 mediates mechanoresponses of the Hippo pathway.

Journal Article Nature · 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 text Link to item Cite

PIP5K1α promotes myogenic differentiation via AKT activation and calcium release.

Journal Article Stem 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 text Link to item Cite

A tiling-deletion-based genetic screen for cis-regulatory element identification in mammalian cells.

Journal Article Nat 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 text Link to item Cite

A Molecular Switch Regulating Cell Fate Choice between Muscle Progenitor Cells and Brown Adipocytes.

Journal Article Dev 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 text Link to item Cite

STAT3 Regulates Self-Renewal of Adult Muscle Satellite Cells during Injury-Induced Muscle Regeneration.

Journal Article Cell 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 text Link to item Cite

A new class of temporarily phenotypic enhancers identified by CRISPR/Cas9-mediated genetic screening.

Journal Article Genome 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 text Link to item Cite

Role of miR-211 in Neuronal Differentiation and Viability: Implications to Pathogenesis of Alzheimer's Disease.

Journal Article Front 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 text Link to item Cite

Plasma microRNA-586 is a new biomarker for acute graft-versus-host disease.

Journal Article Ann 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 text Link to item Cite

Chromatin architecture reorganization during stem cell differentiation.

Journal Article Nature · 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 text Link to item Cite

MicroRNAs 99b-5p/100-5p Regulated by Endoplasmic Reticulum Stress are Involved in Abeta-Induced Pathologies.

Journal Article Front 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 text Link to item Cite

miR-203, a tumor suppressor frequently down-regulated by promoter hypermethylation in rhabdomyosarcoma.

Journal Article J 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 text Link to item Cite

Genome-wide analysis of miRNA signature in the APPswe/PS1ΔE9 mouse model of alzheimer's disease.

Journal Article PLoS 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 text Link to item Cite

Pax3/7BP is a Pax7- and Pax3-binding protein that regulates the proliferation of muscle precursor cells by an epigenetic mechanism.

Journal Article Cell 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 text Link to item Cite

Oxidation-induced intramolecular disulfide bond inactivates mitogen-activated protein kinase kinase 6 by inhibiting ATP binding.

Journal Article Proc 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 text Link to item Cite

SOCS1, SOCS3, and PIAS1 promote myogenic differentiation by inhibiting the leukemia inhibitory factor-induced JAK1/STAT1/STAT3 pathway.

Journal Article Mol 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 text Link to item Cite