Browsing by Subject "Cell lineage"

Now showing 1 - 4 of 4
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    Autophagy modulates CD4+ T-cell lineage recommitment upon pathogen infection
    (Springer Nature, 2020-07) Yang, Kai; Chi, Hongbo; Pediatrics, School of Medicine
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    Cell and matrix response of temporomandibular cartilage to mechanical loading
    (Elsevier, 2016-02) Utreja, Achint; Dyment, Nathaniel A.; Yadav, Sumit; Villa, Max M.; Li, Yingcui; Jiang, Xi; Nanda, Ravindra; Rowe, David W.; Department of Orthodontics and Oral Facial Genetics, School of Dentistry
    OBJECTIVES: The generation of transgenic mice expressing green fluorescent proteins (GFPs) has greatly aided our understanding of the development of connective tissues such as bone and cartilage. Perturbation of a biological system such as the temporomandibular joint (TMJ) within its adaptive remodeling capacity is particularly useful in analyzing cellular lineage progression. The objectives of this study were to determine: (i) if GFP reporters expressed in the TMJ indicate the different stages of cell maturation in fibrocartilage and (ii) how mechanical loading affects cellular response in different regions of the cartilage. DESIGN/METHODS: Four-week-old transgenic mice harboring combinations of fluorescent reporters (Dkk3-eGFP, Col1a1(3.6 kb)-GFPcyan, Col1a1(3.6 kb)-GFPtpz, Col2a1-GFPcyan, and Col10a1-RFPcherry) were used to analyze the expression pattern of transgenes in the mandibular condylar cartilage (MCC). To study the effect of TMJ loading, animals were subjected to forced mouth opening with custom springs exerting 50 g force for 1 h/day for 5 days. Dynamic mineralization and cellular proliferation (EdU-labeling) were assessed in loaded vs control mice. RESULTS: Dkk3 expression was seen in the superficial zone of the MCC, followed by Col1 in the cartilage zone, Col2 in the prehypertrophic zone, and Col10 in the hypertrophic zone at and below the tidemark. TMJ loading increased expression of the GFP reporters and EdU-labeling of cells in the cartilage, resulting in a thickness increase of all layers of the cartilage. In addition, mineral apposition increased resulting in Col10 expression by unmineralized cells above the tidemark. CONCLUSION: The TMJ responded to static loading by forming thicker cartilage through adaptive remodeling.
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    Endocardial HDAC3 is required for myocardial trabeculation
    (Springer Nature, 2024-05-16) Jang, Jihyun; Bentsen, Mette; Kim, Ye Jun; Kim, Erick; Garg, Vidu; Cai, Chen-Leng; Looso, Mario; Li, Deqiang; Pediatrics, School of Medicine
    Failure of proper ventricular trabeculation is often associated with congenital heart disease. Support from endocardial cells, including the secretion of extracellular matrix and growth factors is critical for trabeculation. However, it is poorly understood how the secretion of extracellular matrix and growth factors is initiated and regulated by endocardial cells. We find that genetic knockout of histone deacetylase 3 in the endocardium in mice results in early embryo lethality and ventricular hypotrabeculation. Single cell RNA sequencing identifies significant downregulation of extracellular matrix components in histone deacetylase 3 knockout endocardial cells. Secretome from cultured histone deacetylase 3 knockout mouse cardiac endothelial cells lacks transforming growth factor ß3 and shows significantly reduced capacity in stimulating cultured cardiomyocyte proliferation, which is remarkably rescued by transforming growth factor ß3 supplementation. Mechanistically, we identify that histone deacetylase 3 knockout induces transforming growth factor ß3 expression through repressing microRNA-129-5p. Our findings provide insights into the pathogenesis of congenital heart disease and conceptual strategies to promote myocardial regeneration.
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    Single cell multi-omic analysis identifies a Tbx1-dependent multilineage primed population in murine cardiopharyngeal mesoderm
    (Springer Nature, 2021-11-17) Nomaru, Hiroko; Liu, Yang; De Bono, Christopher; Righelli, Dario; Cirino, Andrea; Wang, Wei; Song, Hansoo; Racedo, Silvia E.; Dantas, Anelisa G.; Zhang, Lu; Cai, Chen-Leng; Angelini, Claudia; Christiaen, Lionel; Kelly, Robert G.; Baldini, Antonio; Zheng, Deyou; Morrow, Bernice E.; Pediatrics, School of Medicine
    The poles of the heart and branchiomeric muscles of the face and neck are formed from the cardiopharyngeal mesoderm within the pharyngeal apparatus. They are disrupted in patients with 22q11.2 deletion syndrome, due to haploinsufficiency of TBX1, encoding a T-box transcription factor. Here, using single cell RNA-sequencing, we now identify a multilineage primed population within the cardiopharyngeal mesoderm, marked by Tbx1, which has bipotent properties to form cardiac and branchiomeric muscle cells. The multilineage primed cells are localized within the nascent mesoderm of the caudal lateral pharyngeal apparatus and provide a continuous source of cardiopharyngeal mesoderm progenitors. Tbx1 regulates the maturation of multilineage primed progenitor cells to cardiopharyngeal mesoderm derivatives while restricting ectopic non-mesodermal gene expression. We further show that TBX1 confers this balance of gene expression by direct and indirect regulation of enriched genes in multilineage primed progenitors and downstream pathways, partly through altering chromatin accessibility, the perturbation of which can lead to congenital defects in individuals with 22q11.2 deletion syndrome.