Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, insulin resistance and inflammation, the pathogenic mechanism of NAFLD poorly understood. Ubiquitin‐specific peptidase 10 (USP10), a member ubiquitin‐specific protease family, involved in environmental stress responses, tumor growth, cellular metabolism. However, role USP10 resistance, inflammation remains largely unexplored. expression was detected livers patients with NAFLD, mice high‐fat diet (HFD)‐induced...

Cranial neural crest cells are an evolutionary innovation of vertebrates for craniofacial development and function, yet the mechanisms that govern cell fate decisions postmigratory cranial remain largely unknown. Using mouse molar as a model, we perform single-cell transcriptome profiling to interrogate diversification cells. We reveal landscape transcriptional heterogeneity define specific cellular domains during progression cell-derived dental lineage diversification, find each domain...

Abstract Mesenchymal stem cells (MSCs) reside in microenvironments, referred to as niches, which provide structural support and molecular signals. Sensory nerves are niche components the homeostasis of tissues such skin, bone marrow hematopoietic system. However, how sensory nerve affects behavior MSCs remains largely unknown. Here we show that is vital for mesenchymal tissue maintenance continuously growing adult mouse incisor. Loss innervation leads disorder a decrease MSCs....

Most existing culture media for cardiac differentiation of human pluripotent stem cells (hPSCs) contain significant amounts albumin. For clinical transplantation applications hPSC-derived cardiomyocytes (hPSC-CMs), culturing in an albumin containing environment raises the concern pathogen contamination and immunogenicity to recipient patients. In addition, batch-to-batch variation may cause inconsistent hPSC differentiation. Here, we demonstrated that antioxidants l-ascorbic acid, trolox,...

ABSTRACT Transcription factors bind to cell-specific cis-regulatory elements, such as enhancers and promoters, initiate much of the gene expression program different biological process. Odontoblast differentiation is a necessary step for tooth formation also governed by complex regulatory network. Our previous in vitro experiments showed that Krüppel-like factor 4 (KLF4) can promote odontoblastic both mouse dental papillary cells (mDPCs) human pulp cells; however, its mechanism remains...

The meninges lie in the interface between skull and brain, harboring lymphatic vasculature progenitor cells (SPCs). How brain communicate remains largely unknown. We found that impaired meningeal lymphatics perfusion drive neurocognitive defects Twist1+/− mice, an animal model of craniosynostosis recapitulating human Saethre-Chotzen syndrome. Loss SPCs leads to deformities elevated intracranial pressure (ICP), whereas transplanting back into mutant mice mitigates through two mechanisms: (1)...

Mesenchymal stem cells (MSCs) reside in niches to maintain tissue homeostasis and contribute repair regeneration. Although the physiological functions of blood lymphatic vasculature are well studied, their regulation MSCs as niche components remains largely unknown. Using adult mouse incisors a model, we uncover role Trp53 regulating vascular composition through THBS2 mesenchymal homeostasis. Loss GLI1+ progeny increases arteries decreases other vessel types. Platelet-derived growth factors...

Abstract Odontoblasts are derived from dental papilla mesenchymal cells and have an important role in defense against bacterial infection, whereas autophagy can recycle long-lived proteins damaged organelles to sustain cellular homeostasis. Thus, this study explores the of odontoblast differentiation with lipopolysaccharide (LPS) stimulation vitro colocalization p-NF- κ B LC3 caries teeth. The odontoblasts was enhanced through LPS stimulation, outcome reflected increased number mineralized...

Cranial neural crest (CNC) cells give rise to bone, cartilage, tendons, and ligaments of the vertebrate craniofacial musculoskeletal complex, as well regulate mesoderm-derived muscle development through cell-cell interactions. Using mouse soft palate a model, we performed an unbiased single-cell RNA-seq analysis investigate heterogeneity lineage commitment CNC derivatives during development. We show that Runx2, known osteogenic regulator, is expressed in CNC-derived perimysial progenitor...

Odontoblasts derive from neural crest–derived odontogenic mesenchymal cells, and they are an important barrier of defense for the host. Survival immunity odontoblasts play roles in protecting dentin-pulp structure. Autophagy can eliminate damaged organelles recycle cellular components to facilitate homeostasis. be activated with external stressors, such as starvation, hypoxia, infection. In this study, role autophagy inflamed was explored, its possible mechanism investigated. Cell viability...

Survival of odontoblasts during infection and inflammation determines prognosis the dental pulp. CD47 is a “self”-label surface marker on viable cells. The aim present study to investigate interaction between CD47, autophagy, apoptosis in inflamed human pulp lipopolysaccharide (LPS)–treated mDPC6T We identified activation autophagy due Furthermore, downregulation correlated with increased patients afflicted either caries and/or pulpitis. also detected colocalization LC3 odontoblasts. In...

Each odontoblast is tightly linked to other odontoblasts. They form a line of defense and are capable withstanding external stimuli, particularly the inflammation caused by caries. Thus, we investigated exosomes derived from odontoblasts as an intercellular mechanism which inflamed protected apoptosis. CD63, exosome marker, was expressed at high levels in caries-affected regions dental pulp. We conducted ex vivo experiment applying different concentrations lipopolysaccharide (LPS)...

Abstract Mouse dental papilla cells (mDPCs) derive from cranial neural crest and maintain mesenchymal stem cell characteristics. The differentiation of into odontoblasts is orchestrated by transcription factors regulating the expression genes whose enhancers are initially inaccessible. However, identity driving emergence odontoblast lineages remains elusive. In this study, we identified SALL1, a factor that was particularly expressed in preodontoblasts, polarizing odontoblasts, secretory...

A comprehensive study of odontoblastic differentiation is essential to understand the process tooth development and achieve ability regeneration in future. Zinc finger E-box-binding homeobox 1 ( Zeb1) a transcription factor expressed various neural crest–derived tissues, including mesenchyme germ. However, its role remains unknown. In this study, we found expression Zeb1 gradually increased during odontoblast vivo, as well induced cultured primary murine dental papilla cells (mDPCs) vitro....

Abstract Objectives Mitophagy is an important mitochondrial quality control mechanism. In this study, we investigated the damage and mitophagy occurred in inflammatory human dental pulp lipopolysaccharide‐stimulated preodontoblasts. Materials Methods tissues preodontoblasts, immunofluorescences Western blot were performed to detect expression of mitophagy‐related proteins, autophagy markers also examined. Reactive oxygen species generated by mitochondria examined MitoSOX. Transmission...

Mammalian tooth crown formation has long served as a model for investigating how patterning and morphogenesis are orchestrated during development. However, the mechanism underlying root remains poorly understood. In this study, we find that Lhx6 labels subpopulation of progenitor cells in apical dental mesenchyme, which is closely associated with furcation Loss leads to number defects, indicating key regulator. Among multiple cellular events regulated by odontoblast fate commitment cells, it...

Rhododendron molle (Ericaceae) is a traditional Chinese medicine, which has been used to treat rheumatism and relieve pain since ancient times. The characteristic grayanoids of this plant have demonstrated be the chemical basis for analgesic activity. Moreover, unlike morphine, these diterpenoids are non-addictive. Grayanoids mainly distribute in leaves, flowers, roots, fruits R. molle, with low content. Currently research on biosynthesis hindered, partially due lack genomic information.In...

Embryonic development and stem cell differentiation are orchestrated by changes in sequential binding of regulatory transcriptional factors to their motifs. These processes invariably accompanied the alternations chromatin accessibility, conformation, histone modification. Odontoblast lineage originates from cranial neural crest cells is crucial dentinogenesis. Our previous work revealed several transcription (TFs) that promote odontoblast differentiation. However, it remains elusive as...

Odontoblast differentiation is an important process during tooth development in which pre-odontoblasts undergo elongation, polarization, and finally become mature secretory odontoblasts. Many factors have been found to regulate the process, our previous studies demonstrated that autophagy plays role promotes odontoblastic inflammatory environment. However, it remains unclear how modulated odontoblast differentiation. In this study, we HDAC6 was involved The capacity of human dental papilla...

Abstract Stem/progenitor cells differentiate into different cell lineages during organ development and morphogenesis. Signaling pathway networks mechanotransduction are important factors to guide the lineage commitment of stem/progenitor craniofacial tissue Here, we used tooth root as a model explore roles FGF signaling well their interaction in regulating progenitor fate decision. We show that Fgfr1 is expressed mesenchymal progeny development. Loss Gli1 + progenitors leads...

Nerves play important roles in organ development and tissue homeostasis. Stem/progenitor cells differentiate into different cell lineages responsible for building the craniofacial organs. The mechanism by which nerves regulate stem/progenitor behavior morphogenesis has not yet been comprehensively explored. Here, we use tooth root mouse as a model to investigate how sensory organogenesis. We show that nerve fibers are enriched dental papilla at initiation of development. Through single...

Macroautophagy/autophagy is critically involved in the process of salivary gland (SG) diseases such as xerostomia, which has a serious impact on quality life. KRT14+ progenitor cells are found to be main progenitors for maintaining ductal homeostasis submandibular SGs. In this study, we investigated role ATG5 SG mice and humans. Human labial glands (LSG) from primary Sjogren's syndrome (pSS) non-pSS patients (normal), (SMG) Atg5flox/flox ; Krt14-Cre (cKO) were used. ATG5+ p62+ detected by...

The homeostasis of adult tissues, such as skin, hair, blood, and bone, requires continuous generation differentiated progeny stem cells. rodent incisor undergoes constant renewal can provide an extraordinary model for studying cells their in tissue homeostasis, cell differentiation injury-induced regeneration. Meanwhile, cellular heterogeneity the mouse also provides opportunity to study cell-cell communication between different types, including interactions niche environment. More...