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18 results on '"Gharibi, Borzo"'

1. GATA3 Mediates a Fast, Irreversible Commitment to BMP4-Driven Differentiation in Human Embryonic Stem Cells

Author

Gunne-Braden, Alexandra, Sullivan, Adrienne, Gharibi, Borzo, Sheriff, Rahuman SM, Maity, Alok, Wang, Yi-Fang, Edwards, Amelia, Jiang, Ming, Howell, Michael, Goldstone, Robert, Wollman, Roy, East, Philip, and Santos, Silvia DM

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Regenerative Medicine, Stem Cell Research, Stem Cell Research - Embryonic - Human, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Bone Morphogenetic Protein 4, Cell Differentiation, GATA3 Transcription Factor, Human Embryonic Stem Cells, Humans, Signal Transduction, BMP4, GATA3, bistability, commitment, differentiation, fate decisions, hESC, positive feedback, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

During early development, extrinsic triggers prompt pluripotent cells to begin the process of differentiation. When and how human embryonic stem cells (hESCs) irreversibly commit to differentiation is a fundamental yet unanswered question. By combining single-cell imaging, genomic approaches, and mathematical modeling, we find that hESCs commit to exiting pluripotency unexpectedly early. We show that bone morphogenetic protein 4 (BMP4), an important differentiation trigger, induces a subset of early genes to mirror the sustained, bistable dynamics of upstream signaling. Induction of one of these genes, GATA3, drives differentiation in the absence of BMP4. Conversely, GATA3 knockout delays differentiation and prevents fast commitment to differentiation. We show that positive feedback at the level of the GATA3-BMP4 axis induces fast, irreversible commitment to differentiation. We propose that early commitment may be a feature of BMP-driven fate choices and that interlinked feedback is the molecular basis for an irreversible transition from pluripotency to differentiation.

Published
2020

2. Adenosine receptor expression and function during mesenchymal stem cell differentiation and osteoblast transdifferentiation

Author

Gharibi, Borzo

Subjects
611
Abstract

The mechanisms involved in osteoblast and adipocyte differentiation from the common progenitor, mesenchymal stem cell (MSC) are not fully understood. The nucleoside, adenosine, exists in all cells and is known to be involved in cell growth, proliferation and apoptosis by interacting with four distinct receptors (Ai, A2A, A2b and A3). The aims of this study was to investigate the expression and function of adenosine receptors in 1) MSCs and as they differentiated into osteoblasts and adipocytes and in 2) mouse 7F2 and human osteoblasts and during their transdifferentiation to adipocytes. Rat MSCs and 7F2 osteoblasts expressed all four adenosine receptors. Osteoblast differentiation was associated with increases in A2A and A2B receptor expression and their activation stimulated the expression of alkaline phosphatase, core binding factor a1 and mineralisation. Adenosine also stimulated adipogenesis (lipid accumulation, peroxisome proliferator-activated receptor, CCAAT/enhancer binding protein a and lipoprotein lipase expression) of MSCs which was accompanied by increased A1 and A2A receptor expression. Transdifferentiation of 7F2 cells to adipocytes was associated with increased Ai, but decreased A2A and A2b receptor expression. Loss of A2 receptors in adipocytes was supported by reduced cAMP and extracellular signal regulated kinase responses to adenosine. Adenosine also stimulated transdifferentiation of human osteoblasts to adipocytes by inducing lipoprotein lipase and inhibiting alkaline phosphatase and osteocalcin expression. Overexpression of Ai receptors in 7F2 cells stimulated adipogenesis (lipid accumulation and lipoprotein lipase expression) whereas overexpression of A2b receptors stimulated alkaline phophatase expression and inhibited adipogenesis. These results show that adenosine receptor expression and function is involved in lineage specific differentiation or transdifferentiation A2B receptors are associated with MSCs and osteoblasts and Ai receptors with adipocytes. Targeting adenosine signal pathways may thus be useful as an adjunct therapy for the prevention or treatment of conditions in which there is insufficient bone or excessive adipocyte formation.

Published
2010

4. A FGF2-mediated incoherent feedforward loop induces Erk inhibition and promotes naïve pluripotency

Author

Gharibi, Borzo, primary, Gonçalves, Emanuel, additional, Nashun, Buhe, additional, Montoya, Alex, additional, Mankalow, Katherine, additional, Strohbuecker, Stephanie, additional, Sheriff, Rahuman S M, additional, Cicarrelli, Alessandro, additional, Carvalho, Joana, additional, Nye, Emma, additional, Kramer, Holger, additional, Rosewell, Ian, additional, Hajkova, Petra, additional, Beltrao, Pedro, additional, and Santos, Silvia D. M., additional

Published
2020
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5. Cellular differentiation, bioactive and mechanicalproperties of experimental light-curing pulpprotection materials

Author

Sauro, Salvatore, Babbar, Ashvin, Gharibi, Borzo, Feitosa, Victor Pinheiro, Carvalho, Ricardo Marins, Rodrigues, Lidiany Karla Azevedo, Banerjee, Avijit, and Watson, Timothy

Subjects
Zinco, Zinc, Materials Testing, Teste de Materiais
Abstract

Objective. Materials for pulp protection should have therapeutic properties in order to stim-ulate remineralization and pulp reparative processes. The aim of this study was to evaluatethe mechanical properties, biocompatibility, cell differentiation and bioactivity of experi-mental light-curable resin-based materials containing bioactive micro-fillers.Methods. Four calcium-phosphosilicate micro-fillers were prepared and incorporated into aresin blend: 1) Bioglass 45S5 (BAG); 2) zinc-doped bioglass (BAG-Zn); 3) TCP-modified cal-cium silicate ( -CS); 4) zinc-doped -CS ( -CS-Zn). These experimental resins were testedfor flexural strength (FS) and fracture toughness (FT) after 24 h and 30-day storage in sim-ulated body fluid (SBF). Cytotoxicity was evaluated using MTT assay, while bioactivity wasevaluated using mineralization and gene expression assays (Runx-2 & ALP).Results. The lowest FS and FT at 24 h was attained with -CS resin, while all the other testedmaterials exhibited a decrease in FS after prolonged storage in SBF. -CS-Zn maintained astable FT after 30-day SBF aging. Incorporation of bioactive micro-fillers had no negativeeffect on the biocompatibility of the experimental materials tested in this study. The inclu-sion of zinc-doped fillers significantly increased the cellular remineralization potential andexpression of the osteogenic genes Runx2 and ALP (p < 0.05).

Published
2018

16. Adenosine receptor expression and function during mesenchymal stem cell differentiation and osteoblast transdifferentiation

Author

Gharibi, Borzo

Subjects
TA
Abstract

The mechanisms involved in osteoblast and adipocyte differentiation from the common progenitor, mesenchymal stem cell (MSC) are not fully understood. The nucleoside, adenosine, exists in all cells and is known to be involved in cell growth, proliferation and apoptosis by interacting with four distinct receptors (Ai, A2A, A2b and A3). The aims of this study was to investigate the expression and function of adenosine receptors in 1) MSCs and as they differentiated into osteoblasts and adipocytes and in 2) mouse 7F2 and human osteoblasts and during their transdifferentiation to adipocytes. Rat MSCs and 7F2 osteoblasts expressed all four adenosine receptors. Osteoblast differentiation was associated with increases in A2A and A2B receptor expression and their activation stimulated the expression of alkaline phosphatase, core binding factor a1 and mineralisation. Adenosine also stimulated adipogenesis (lipid accumulation, peroxisome proliferator-activated receptor, CCAAT/enhancer binding protein a and lipoprotein lipase expression) of MSCs which was accompanied by increased A1 and A2A receptor expression. Transdifferentiation of 7F2 cells to adipocytes was associated with increased Ai, but decreased A2A and A2b receptor expression. Loss of A2 receptors in adipocytes was supported by reduced cAMP and extracellular signal regulated kinase responses to adenosine. Adenosine also stimulated transdifferentiation of human osteoblasts to adipocytes by inducing lipoprotein lipase and inhibiting alkaline phosphatase and osteocalcin expression. Overexpression of Ai receptors in 7F2 cells stimulated adipogenesis (lipid accumulation and lipoprotein lipase expression) whereas overexpression of A2b receptors stimulated alkaline phophatase expression and inhibited adipogenesis. These results show that adenosine receptor expression and function is involved in lineage specific differentiation or transdifferentiation A2B receptors are associated with MSCs and osteoblasts and Ai receptors with adipocytes. Targeting adenosine signal pathways may thus be useful as an adjunct therapy for the prevention or treatment of conditions in which there is insufficient bone or excessive adipocyte formation.

17. Adenosine receptor expression and function during mesenchymal stem cell differentiation and osteoblast transdifferentiation.

Author

Gharibi, Borzo and Gharibi, Borzo

Abstract

The mechanisms involved in osteoblast and adipocyte differentiation from the common progenitor, mesenchymal stem cell (MSC) are not fully understood. The nucleoside, adenosine, exists in all cells and is known to be involved in cell growth, proliferation and apoptosis by interacting with four distinct receptors (Ai, A2A, A2b and A3). The aims of this study was to investigate the expression and function of adenosine receptors in 1) MSCs and as they differentiated into osteoblasts and adipocytes and in 2) mouse 7F2 and human osteoblasts and during their transdifferentiation to adipocytes. Rat MSCs and 7F2 osteoblasts expressed all four adenosine receptors. Osteoblast differentiation was associated with increases in A2A and A2B receptor expression and their activation stimulated the expression of alkaline phosphatase, core binding factor a1 and mineralisation. Adenosine also stimulated adipogenesis (lipid accumulation, peroxisome proliferator-activated receptor, CCAAT/enhancer binding protein a and lipoprotein lipase expression) of MSCs which was accompanied by increased A1 and A2A receptor expression. Transdifferentiation of 7F2 cells to adipocytes was associated with increased Ai, but decreased A2A and A2b receptor expression. Loss of A2 receptors in adipocytes was supported by reduced cAMP and extracellular signal regulated kinase responses to adenosine. Adenosine also stimulated transdifferentiation of human osteoblasts to adipocytes by inducing lipoprotein lipase and inhibiting alkaline phosphatase and osteocalcin expression. Overexpression of Ai receptors in 7F2 cells stimulated adipogenesis (lipid accumulation and lipoprotein lipase expression) whereas overexpression of A2b receptors stimulated alkaline phophatase expression and inhibited adipogenesis. These results show that adenosine receptor expression and function is involved in lineage specific differentiation or transdifferentiation A2B receptors are associated with MSCs and osteoblasts and Ai receptors wi

18. Adenosine receptor expression and function during mesenchymal stem cell differentiation and osteoblast transdifferentiation.

Author

Gharibi, Borzo and Gharibi, Borzo

Abstract

The mechanisms involved in osteoblast and adipocyte differentiation from the common progenitor, mesenchymal stem cell (MSC) are not fully understood. The nucleoside, adenosine, exists in all cells and is known to be involved in cell growth, proliferation and apoptosis by interacting with four distinct receptors (Ai, A2A, A2b and A3). The aims of this study was to investigate the expression and function of adenosine receptors in 1) MSCs and as they differentiated into osteoblasts and adipocytes and in 2) mouse 7F2 and human osteoblasts and during their transdifferentiation to adipocytes. Rat MSCs and 7F2 osteoblasts expressed all four adenosine receptors. Osteoblast differentiation was associated with increases in A2A and A2B receptor expression and their activation stimulated the expression of alkaline phosphatase, core binding factor a1 and mineralisation. Adenosine also stimulated adipogenesis (lipid accumulation, peroxisome proliferator-activated receptor, CCAAT/enhancer binding protein a and lipoprotein lipase expression) of MSCs which was accompanied by increased A1 and A2A receptor expression. Transdifferentiation of 7F2 cells to adipocytes was associated with increased Ai, but decreased A2A and A2b receptor expression. Loss of A2 receptors in adipocytes was supported by reduced cAMP and extracellular signal regulated kinase responses to adenosine. Adenosine also stimulated transdifferentiation of human osteoblasts to adipocytes by inducing lipoprotein lipase and inhibiting alkaline phosphatase and osteocalcin expression. Overexpression of Ai receptors in 7F2 cells stimulated adipogenesis (lipid accumulation and lipoprotein lipase expression) whereas overexpression of A2b receptors stimulated alkaline phophatase expression and inhibited adipogenesis. These results show that adenosine receptor expression and function is involved in lineage specific differentiation or transdifferentiation A2B receptors are associated with MSCs and osteoblasts and Ai receptors wi

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