Biology subjects

Wu, J.

Publications and source records attributed to Wu, J..

At least 685 records · Page 38Linked to original sources

bioRxiv2021

New metabolic alterations and predictive marker pipecolic acid in sera for esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with dismal prognosis. Although several serum metabolomic investigations have been reported, ESCC tumor-associated metabolic alterations along with predictive biomarkers in sera were not defined. Here we enrolled 34 treatment-naive ESCC patients and collected their pre-and post-esophagectomy sera together with sera from 34 healthy volunteers for metabolomic survey. Our comprehensive analysis discerned ESCC tumor-associated metabolic alterations as represented by a panel of 12 serum metabolites. Notably, postoperative abrosia and parenteral nutrition significantly perturbed the serum metabolome. Furthermore, we performed examination using sera from carcinogen-induced mice at dysplasia and ESCC stages, and identified three ESCC tumor-associated metabolites conserved between mice and humans. Notably, among these metabolites, pipecolic acid was progressively increased in mouse sera from dysplasia to cancerization, and it could accurately discriminate between mice at dysplasia stage and healthy control mice. Furthermore, this metabolite was essential for ECSS cells to oppose oxidative stress-induced DNA damage and cell proliferation arrest. Together, this study uncovered 12 ESCC tumor-associated serum metabolites with potential for monitoring therapeutic efficacy and disease relapse, presented evidence for refining parenteral nutrition composition, and highlighted serum pipecolic acid as an attractive biomarker for prediction of ESCC tumorigenesis.

cancer biology↗

bioRxiv2021

Phase separation of RNA-binding protein promotes polymerase engagement and transcription

An RNA-involved phase-separation model has been proposed for transcription control. Yet, the molecular links that connect RNA binding to the transcription machinery remain missing. Here we find RNA-binding proteins (RBPs) constitute half of the chromatin proteome in embryonic stem cells (ESCs), and some are colocalized with RNA polymerase (Pol) II at promoters and enhancers. Biochemical analyses of representative RBPs--such as PSPC1 and PTBP1--show that the paraspeckle protein PSPC1 not only prevents the RNA-induced premature release of Pol II, and also makes use of RNA as multivalent molecules to promote Pol II engagement and activity, by enhancing the phase separation and subsequent phosphorylation and release of polymerase condensates. In ESCs, auxin-induced acute degradation of PSPC1 leads to genome-wide defects in Pol II phosphorylation and chromatin-binding and nascent transcription. We propose that the synergistic interplay of RBPs and RNA aids in the rate-limiting step of polymerase condensate formation to promote active transcription.

biochemistry↗

bioRxiv2021

Structural variant selection for high-altitude adaptation using single-molecule long-read sequencing

Structural variants (SVs) can be important drivers of human adaptation with strong effects, but previous studies have focused primarily on common variants with weak effects. Here, we used large-scale single-molecule long-read sequencing of 320 Tibetan and Han samples, to show that SVs are key drivers of selection under high-altitude adaptation. We expand the landscape of global SVs, apply robust models of selection and population differentiation combining SVs, SNPs and InDels, and use epigenomic analyses to predict driver enhancers, target genes, upstream regulators, and biological functions, which we validate using enhancer reporter and DNA pull-down assays. We reveal diverse Tibetan-specific SVs affecting the cis- and trans-regulatory circuitry of diverse biological functions, including hypoxia response, energy metabolism, lung function, etc. Our study greatly expands the global SV landscape, reveals the central role of gene-regulatory circuitry rewiring in human adaptation, and illustrates the diverse functional roles that SVs can play in human biology.

genomics↗

bioRxiv2021

Massive loss of transcription factors and the initial diversification of placental mammals

As one of the most successful categories of organisms, mammals occupy a variety of niches on earth as a result of macroevolution. Transcription factors (TFs), the basic regulators of gene expression, may also evolve during mammalian phenotypic diversification and macroevolution. To examine the relationship between TFs and mammalian macroevolution, we analyzed 140,821 de novo-identified TFs and their birth and death histories from 96 mammalian species. Gene tree vs. species tree reconciliation revealed that mammals experienced an upsurge in TF losses around 100 million years ago and also near the K-Pg boundary, thus implying a relationship with the divergence of placental animals. From approximately 100 million years ago to the present, losses dominated TF events without a significant change in TF gains. To quantify the effects of this TF pruning on mammalian macroevolution, we analyzed rates of molecular evolution and expression profiles of regulated target genes. Surprisingly, TF loss decelerated, rather than accelerated, molecular evolutionary rates of their target genes, suggesting increased functional constraints. Furthermore, an association study revealed that massive TF losses are significantly positively correlated with solitary behavior, nocturnality, reproductive-seasonality and insectivory life history traits, possibly through rewiring of regulatory networks.

evolutionary biology↗

bioRxiv2021

Occurrence of COVID-19 symptoms during SARS-CoV-2 infection defines waning of humoral immunity

Approximately half of the SARS-CoV-2 infections occur without apparent symptoms, raising questions regarding long-term humoral immunity in asymptomatic individuals. Plasma levels of immunoglobulin G (IgG) and M (IgM) against the viral spike or nucleoprotein were determined for 25,091 individuals enrolled in a surveillance program in Wuhan, China. We compared 405 asymptomatic individuals with 459 symptomatic COVID-19 patients. The well-defined duration of the SARS-CoV-2 endemic in Wuhan allowed a side-by-side comparison of antibody responses following symptomatic and asymptomatic infections without subsequent antigen re-exposure. IgM responses rapidly declined in both groups. However, both the prevalence and durability of IgG responses and neutralizing capacities correlated positively with symptoms. Regardless of sex, age, and body weight, asymptomatic individuals lost their SARS-CoV-2-specific IgG antibodies more often and rapidly than symptomatic patients. These findings have important implications for immunity and favour immunization programs including individuals after asymptomatic infections. One-Sentence SummaryPrevalence and durability of SARS-CoV-2-specific IgG responses and neutralizing capacities correlate with COVID-19 symptoms.

immunology↗

bioRxiv2021

Epigallocatechin Gallate from Green Tea Effectively Blocks Infection of SARS-CoV-2 and New Variants by Inhibiting Spike Binding to ACE2 Receptor

As the COVID-19 pandemic rages on, the new SARS-CoV-2 variants have emerged in the different regions of the world. These newly emerged variants have mutations in their spike (S) protein that may confer resistance to vaccine-elicited immunity and existing neutralizing antibody therapeutics. Therefore, there is still an urgent need of safe, effective, and affordable agents for prevention/treatment of SARS-CoV-2 and its variant infection. Here, we demonstrated that green tea beverage (GTB) or its major ingredient, epigallocatechin gallate (EGCG), were highly effective in inhibiting infection of live SARS-CoV-2 and human coronavirus (HCoV OC43). In addition, infection of the pseudoviruses with spikes of the new variants (UK-B.1.1.7, SA-B.1.351, and CA-B.1.429) was efficiently blocked by GTB or EGCG. Among the 4 active green tea catechins at noncytotoxic doses, EGCG was the most potent in the action against the viruses. The highest inhibitory activity was observed when the viruses or the cells were pre-incubated with EGCG prior to the infection. Mechanistic studies revealed that EGCG blocked infection at the entry step through interfering with the engagement of the receptor binding domain (RBD) of the viral spikes to angiotensin-converting enzyme 2 (ACE2) receptor of the host cells. These data support further clinical evaluation and development of EGCG as a novel, safe, and cost-effective natural product for prevention/treatment of SARS-CoV-2 transmission and infection.

microbiology↗

bioRxiv2021

An Off-the-Shelf Bioadhesive Patch for Sutureless Repair of Gastrointestinal Defects

Surgical sealing and repair of injured and resected gastrointestinal (GI) organs are critical requirements for successful treatment and tissue healing. Despite being the standard of care, hand-sewn closure of GI defects using sutures faces various limitations and challenges. The process remains technically complicated and time-consuming. The needle-piercing and pointwise closure also inflict tissue damage and stress concentration, raising the risk of local failure and subsequent anastomotic leaks. To address these limitations and challenges, we introduce an off-the-shelf bioadhesive GI patch capable of atraumatic, rapid, robust, and sutureless repair of GI defects. The GI patch synergistically integrates a non-adhesive top layer and a dry bioadhesive bottom layer, resulting in a thin, flexible, transparent, and ready to use dressing with tissue-matching mechanical properties. Rapid, robust, and sutureless sealing capability of the GI patch is systematically characterized based on various standard tests in ex vivo porcine GI organ models. In vitro and in vivo rat models are utilized to validate biocompatibility and biodegradability of the GI patch including comprehensive cytotoxicity, histopathology, immunofluorescence, and blood analyses. To validate the GI patchs efficacy in a clinically relevant setting, we demonstrate successful sutureless in vivo sealing and healing of GI defects; namely in rat stomach and colon, and porcine colon injury models. The proposed GI patch not only provides a promising alternative to suture for repair of GI defects but also offers potential clinical opportunities in the treatment and repair of other organs. One Sentence SummaryAn off-the-shelf bioadhesive patch is introduced for facile sutureless repair of gastrointestinal defects, addressing various limitations of conventional suture-based treatments.

bioengineering↗

bioRxiv2021

In vivo co-registered hybrid-contrast imaging by successive photoacoustic tomography and magnetic resonance imaging

Magnetic resonance imaging (MRI) and photoacoustic tomography (PAT) are two advanced imaging modalities that offer two distinct image contrasts: MRI has a multi-parameter contrast mechanism that provides excellent anatomical soft tissue contrast, whereas PAT is capable of mapping tissue physiological metabolism and exogenous contrast agents with optical specificity. Attempts have been made to integrate these two modalities, but rigid and reliable registration of the images for in vivo imaging is still challenging. In this paper, we present a complete hardware-software solution for the successive acquisition and co-registration of PAT and MRI images in in vivo animal studies. Based on commercial PAT and MRI scanners, our solution includes a 3D-printed dual-modality animal imaging bed, a 3-D spatial image co-registration algorithm with bi-model markers, and a robust modality switching protocol for in vivo imaging studies. Using the proposed solution, we successfully demonstrated co-registered hybrid-contrast PAT-MRI imaging that simultaneously display multi-scale anatomical, functional and molecular characteristics on healthy and cancerous living mice. Week-long longitudinal dual-modality imaging of tumor development reveals information on size, border, vascular pattern, blood oxygenation, and molecular probe metabolism of the tumor micro-environment at the same time. Additionally, by incorporating soft-tissue information in the co-registered MRI image, we further show that PAT image quality could be enhanced by MRI-guided light fluence correction. The proposed methodology holds the promise for a wide range of pre-clinical research applications that benefit from the PAT-MRI dual-modality image contrast.

bioengineering↗

bioRxiv2021

Episodic memory in aspects of brain information transfer by resting-state network topology

Studies suggest that resting-state functional connectivity conveys cognitive information; also, activity flow mediates cognitive information transfer. However, the exact mechanism of interregional interactions underlying episodic memory remains unclear. We performed a combined analysis of task-evoked activity and resting-state functional connectivity by activity flow mapping to estimate the information transfer mechanism of episodic memory. We found that the cognitive control and attentional networks were the most recruited structures in information transfers during both encoding and retrieval processes; these networks were correlated with task-evoked activation. Differences in information transfer intensity between encoding and retrieval mainly existed in the visual, somatomotor and hippocampal systems. Furthermore, information transfer showed high predictive power for episodic memory ability and mediated relationships between task-evoked activation and memory performance. Additional analysis indicated that structural connectivity had a transportive role in information transfer. Finally, our study presented the information transfer mechanism of episodic memory from multiple neural perspectives.

neuroscience↗

bioRxiv2021

Single-cell transcriptomics reveal cell type-specific molecular changes and altered intercellular communications in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a common and heterogeneous respiratory disease, the molecular complexity of which remains poorly understood, as well as the mechanisms by which aging and smoking facilitate COPD development. Here, using single-cell RNA sequencing of more than 65,000 cells from COPD and age-stratified control lung tissues of donors with different smoking histories, we identified monocytes, club cells, and macrophages as the most disease-, aging-, and smoking-relevant cell types, respectively. Notably, we found these highly cell-type specific changes under different conditions converged on cellular dysfunction of the alveolar epithelium. Deeper investigations revealed that the alveolar epithelium damage could be attributed to the abnormally activated monocytes in COPD lungs, which could be amplified via exhaustion of club cell stemness as ages. Moreover, the enhanced intercellular communications in COPD lungs as well as the pro-inflammatory interaction between macrophages and endothelial cells indued by smoking could facilitate signaling between monocyte and the alveolar epithelium. Our findings complement the existing model of COPD pathogenesis by emphasizing the contributions of the previously less appreciated cell types, highlighting their candidacy as potential therapeutic targets for COPD.

pathology↗

bioRxiv2021

FAM114A1 Influences Cardiac Fibrosis by Regulating Angiotensin II Signaling in Cardiac Fibroblasts

Cardiac fibrosis, a primary contributor to heart failure (HF) and sudden death, is considered as an important target for HF therapy. However, the signaling pathways that govern cardiac fibroblast (CF) function during cardiac fibrosis have not been fully elucidated. Here, we found that a functionally unannotated human myocardial infarction (MI) associated gene, family with sequence similarity 114 member A1 (FAM114A1), is induced in failing human and mouse hearts compared to non-failing hearts. Homozygous knockout of Fam114a1 (Fam114a1-/-) in the mouse genome reduces cardiac hypertrophy and fibrosis while significantly restores cardiac function in angiotensin (Ang) II- and MI-induced HF mouse models. Fam114a1 deletion antagonizes Ang II induced inflammation and oxidative stress. Using isolated mouse primary CFs in wild type and Fam114a1-/- mice, we found that FAM114A1 is a critical autonomous factor for CF proliferation, activation, and migration. We discovered that FAM114A1 interacts with angiotensin receptor associated protein (AGTRAP) and regulates the expression of angiotensin type 1 receptor (AT1R) and downstream Ang II signaling transduction, and subsequently influences pro-fibrotic response. Using RNA-Seq in mouse primary CFs, we identified differentially expressed genes including extracellular matrix proteins such as Adamts15. RNAi-mediated inactivation of Adamts15 attenuates CF activation and collagen deposition. Our results indicate that FAM114A1 regulates Ang II signaling and downstream pro-fibrotic and pro-inflammatory gene expression, thereby activating cardiac fibroblasts and augmenting pathological cardiac remodeling. These findings provide novel insights into regulation of cardiac fibrosis and identify FAM114A1 as a new therapeutic target for treatment of cardiac disease. SignificanceCardiac fibrosis is a hallmark of heart failure and angiotensin II signaling promotes pro-fibrotic response in the heart. This study is a pioneering investigation of the role of a functionally unknown protein FAM114A1. We show that FAM114A1 expression is induced in human and mouse failing hearts. Genetic ablation of FAM114A1 can effectively reduce cardiac fibrosis and pathological remodeling. Isolated cardiac fibroblasts from Fam114a1 knockout mice show reduced response to Ang II stimulation and compromised myofibroblast activation. Mechanistically, FAM114A1 binds to AGTRAP and influences AT1R protein expression, thereby enhancing angiotensin II signaling and pro-fibrotic response. Thus, FAM114A1 is a novel factor that modulates cardiac fibrosis and pharmacological inhibition of FAM114A1 may be a therapeutic strategy for the treatment of heart disease.

pathology↗

bioRxiv2021

Rice NIN-LIKE PROTEIN 3 plays a significant role in nitrogen use efficiency and grain yield under nitrate-sufficient conditions

Nitrogen (N) is an essential macronutrient for crop growth and yield, but excessive application of N fertilizer has caused serious environmental pollution and greatly increased the cost of agricultural production. One of the effective and economical solutions to this dilemma is to improve the N use efficiency (NUE) of crops. Although some components involved in regulating NUE have been identified, the underlying molecular mechanism remains largely elusive in rice. Here we report that the OsNLP3 (NIN-like protein 3) is an important regulator in NUE and grain yield under nitrate-sufficient conditions. Both NUE and grain yield were significantly improved by enhanced OsNLP3 expression in the field, but reduced in osnlp3 mutants. The expression of OsNLP3 responds to both nitrate and ammonium, while OsNLP3 nuclear retention is only induced by nitrate, not by ammonium. OsNLP3 regulates the expression of a set of genes involved in N transport and assimilation by directly binding to the nitrate-responsive cis-element in the promoters of these genes. Our study demonstrates that OsNLP3 is significant for the regulation of NUE and grain yield, particularly in nitrate-rich conditions, thus providing a candidate for improving NUE and grain yield in rice.

plant biology↗

bioRxiv2021

AGL16 negatively modulates stress response to balance with growth

Sensile plants constantly experience environmental stresses in nature. They must have evolved effective mechanisms to balance growth with stress response. Here we report the MADS-box transcription factor AGL16 acting as a negative regulator in stress response. Loss-of-AGL16 confers resistance to salt stress in seed germination, root elongation, and soil-grown plants, while elevated AGL16 expression confers the opposite phenotypes compared with wild type. However, the sensitivity to ABA in seed germination is inversely correlated with AGL16 expression level. Transcriptomic comparison revealed that the improved salt resistance of agl16 mutant was largely attributed to enhanced expression of stress responsive transcriptional factors and genes involved in ABA signaling and ion homeostasis. We further demonstrated that AGL16 directly binds to the CArG motifs in the promoter of HKT1;1, HsfA6a, and MYB102 and represses their expression. Genetic analyses with double mutants also support that HsfA6a and MYB102 are target genes of AGL16. Taken together, our results show that AGL16 acts as negative regulator transcriptionally suppressing key components in stress response and may play a critical role in balancing stress response with growth.

plant biology↗

bioRxiv2021

Targeting Gys1 with AAV-SaCas9 decreases pathogenic polyglucosan bodies and neuroinflammation in Adult Polyglucosan Body and Lafora disease mouse models

Many adult and most childhood neurological diseases have a genetic basis. CRISPR/Cas9 biotechnology holds great promise in neurological therapy, pending the clearance of major delivery, efficiency and specificity hurdles. We apply CRISPR/Cas9 genome editing in its simplest modality, namely inducing gene sequence disruption, to one adult and one pediatric disease. Adult polyglucosan body disease is a neurodegenerative disease resembling amyotrophic lateral sclerosis. Lafora disease is a severe late childhood onset progressive myoclonus epilepsy. The pathogenic insult in both is formation in the brain of glycogen with overlong branches, which precipitates and accumulates into polyglucosan bodies that drive neuroinflammation and neurodegeneration. We packaged Staphylococcus aureus Cas9 and a guide RNA targeting the glycogen synthase gene Gys1 responsible for brain glycogen branch elongation in AAV9 virus, which we delivered by neonatal intracerebroventricular injection to one mouse model of adult polyglucosan body disease and two mouse models of Lafora disease. This resulted, in all three models, in editing of approximately 17% of Gys1 alleles and a similar extent of reduction of Gys1 mRNA across the brain. The latter led to approximately 50% reductions of GYS1 protein, of abnormal glycogen accumulation and of polyglucosan bodies, as well as corrections of neuroinflammatory markers in all three models. Our work represents proof of principle for virally-delivered CRISPR/Cas9 neurotherapeutics in an adult-onset (adult polyglucosan body) and a childhood-onset (Lafora) neurological diseases.

neuroscience↗

bioRxiv2021

Severe deficiency of voltage-gated sodium channel NaV1.2 elevates neuronal excitability in adult mice

Scn2a encodes voltage-gated sodium channel NaV1.2, which mediates neuronal firing. The current paradigm suggests that NaV1.2 gain-of-function variants enhance neuronal excitability resulting in epilepsy, whereas NaV1.2 deficiency impairs neuronal excitability contributing to autism. In this paradigm, however, why about a third of patients with NaV1.2 deficiency still develop seizures remains a mystery. Here we challenge the conventional wisdom, reporting that neuronal excitability is increased with severe NaV1.2 deficiency. Using a unique gene-trap knockout mouse model of Scn2a, we found enhanced intrinsic excitabilities of principal neurons in the cortico-striatal circuit, known to be involved in Scn2a-related seizures. This increased excitability is autonomous, and is reversible by genetic restoration of Scn2a expression in adult mice. Mechanistic investigation reveals a compensatory downregulation of potassium channels including KV1.1, which could be targeted to alleviate neuronal hyperexcitability. Our unexpected findings may explain NaV1.2 deficiency-related epileptic seizures in humans and provide molecular targets for potential interventions. TEASERSevere NaV1.2 deficiency results in neuronal hyperexcitability via the compensatory downregulation of potassium channels. HIGHLIGHTSO_LISevere NaV1.2 deficiency results in enhanced excitability of medium spiny neurons (MSNs) and pyramidal neurons in adult mice; C_LIO_LIIncreased neuronal excitability in MSNs is accompanied by elevated voltage threshold; C_LIO_LINaV1.2 deficiency-related hyperexcitability is reversible with the restoration of Scn2a expression, and is autonomous; C_LIO_LIThe expression of the KV1.1 channel has a compensatory reduction in neurons with NaV1.2 deficiency, and KV channels openers normalize the neuronal excitability; C_LIO_LIThe enhanced excitability in brain slices translates to elevated in vivo firing commonly associated with seizures. C_LI

neuroscience↗

bioRxiv2021

Multicellular immune hubs and their organization in MMRd and MMRp colorectal cancer

Immune responses to cancer are highly variable, with mismatch repair-deficient (MMRd) tumors exhibiting more anti-tumor immunity than mismatch repair-proficient (MMRp) tumors. To understand the rules governing these varied responses, we transcriptionally profiled 371,223 cells from colorectal tumors and adjacent normal tissues of 28 MMRp and 34 MMRd patients. Analysis of 88 cell subsets and their 204 associated gene expression programs revealed extensive transcriptional and spatial remodeling across tumors. To discover hubs of interacting malignant and immune cells, we identified expression programs in different cell types that co-varied across patient tumors and used spatial profiling to localize coordinated programs. We discovered a myeloid cell-attracting hub at the tumor-luminal interface associated with tissue damage, and an MMRd-enriched immune hub within the tumor, with activated T cells together with malignant and myeloid cells expressing T-cell-attracting chemokines. By identifying interacting cellular programs, we thus reveal the logic underlying spatially organized immune-malignant cell networks.

cancer biology↗

bioRxiv2021

SAILER: Scalable and Accurate Invariant Representation Learning for Single-Cell ATAC-Seq Processing and Integration

MotivationSingle-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) provides new opportunities to dissect epigenomic heterogeneity and elucidate transcriptional regulatory mechanisms. However, computational modelling of scATAC-seq data is challenging due to its high dimension, extreme sparsity, complex dependencies, and high sensitivity to confounding factors from various sources. ResultsHere we propose a new deep generative model framework, named SAILER, for analysing scATAC-seq data. SAILER aims to learn a low-dimensional nonlinear latent representation of each cell that defines its intrinsic chromatin state, invariant to extrinsic confounding factors like read depth and batch effects. SAILER adopts the conventional encoder-decoder framework to learn the latent representation but imposes additional constraints to ensure the independence of the learned representations from the confounding factors. Experimental results on both simulated and real scATAC-seq datasets demonstrate that SAILER learns better and biologically more meaningful representations of cells than other methods. Its noise-free cell embeddings bring in significant benefits in downstream analyses: Clustering and imputation based on SAILER result in 6.9% and 18.5% improvements over existing methods, respectively. Moreover, because no matrix factorization is involved, SAILER can easily scale to process millions of cells. We implemented SAILER into a software package, freely available to all for large-scale scATAC-seq data analysis. AvailabilityThe software is publicly available at https://github.com/uci-cbcl/SAILER Contactjingz31@uci.edu and xhx@uci.edu

bioinformatics↗

bioRxiv2021

ACVR1R206H increases osteogenic/ECM gene expression and impairs myofiber formation in human skeletal muscle stem cells

Abnormalities in skeletal muscle repair lead to poor function and complications such as scarring or heterotopic ossification (HO). Here, we use fibrodysplasia ossificans progressiva (FOP), a disease of progressive HO caused by ACVR1R206H (Activin receptor type-1 receptor) mutation, to elucidate how ACVR1 affects skeletal muscle repair. Rare and unique primary FOP human muscle stem cells (Hu-MuSCs) isolated from cadaveric skeletal muscle demonstrated increased ECM marker expression, and showed skeletal muscle-specific impaired engraftment and regeneration ability. Human induced pluripotent stem cell (iPSC)-derived muscle stem/progenitor cells (iMPCs) Single cell transcriptome analyses from FOP also revealed unusually increased ECM and osteogenic marker expression compared to control iMPCs. These results show that iMPCs can recapitulate many aspects of Hu-MuSCs for detailed in vitro study, that ACVR1 is a key regulator of Hu-MuSC function and skeletal muscle repair; and that ACVR1 activation in iMPCs or Hu-MuSCs contributes to HO by changing the local tissue environment.

cell biology↗