Dysregulated lineage commitment of mesenchymal stem cells(MSCs)contributes to impaired bone formation and an imbalance between adipogenesis and osteogenesis during skeletal aging and osteoporosis.The intrinsic cellula...Dysregulated lineage commitment of mesenchymal stem cells(MSCs)contributes to impaired bone formation and an imbalance between adipogenesis and osteogenesis during skeletal aging and osteoporosis.The intrinsic cellular mechanism that regulates MSC commitment remains unclear.Here,we identified Cullin 4B(CUL4B)as a critical regulator of MSC commitment.CUL4B is expressed in bone marrow MSCs(BMSCs)and downregulated with aging in mice and humans.Conditional knockout of Cul4b in MSCs resulted in impaired postnatal skeletal development with low bone mass and reduced bone formation.Moreover,depletion of CUL4B in MSCs aggravated bone loss and marrow adipose accumulation during natural aging or after ovariectomy.In addition,CUL4B deficiency in MSCs reduced bone strength.Mechanistically,CUL4B promoted osteogenesis and inhibited adipogenesis of MSCs by repressing KLF4 and C/EBPδexpression,respectively.The CUL4B complex directly bound to Klf4 and Cebpd and epigenetically repressed their transcription.Collectively,this study reveals CUL4B-mediated epigenetic regulation of the osteogenic or adipogenic commitment of MSCs,which has therapeutic implications in osteoporosis.展开更多
It is estimated that infertility impacts 8%-12%of reproductive-aged couples worldwide.Female infertility accounts for 37%of causes among infertile couples,and ovulatory dysfunction is regarded as its most common facto...It is estimated that infertility impacts 8%-12%of reproductive-aged couples worldwide.Female infertility accounts for 37%of causes among infertile couples,and ovulatory dysfunction is regarded as its most common factor.1 cUL4B belongs to the Cullin family,whose members are the scaffolding proteins of Cullin-RING E3 ligases(CRLs).Human CUL4B gene mutations result in X-linked mental retardation syndromes.In addition to mental retardation,patients have symptoms such as short stature,obesity,and hypogonadism.展开更多
Thermoresponsive polymers with simultaneous biodegradability and signal“self-reporting”outputs that meet for advanced applications are hard to obtain.To address this issue,we developed fluorescence signal“self-repo...Thermoresponsive polymers with simultaneous biodegradability and signal“self-reporting”outputs that meet for advanced applications are hard to obtain.To address this issue,we developed fluorescence signal“self-reporting”biodegradable thermoresponsive polycarbonates through the immortal copolymerization of CO_(2)and oligoethylene glycol monomethyl ether-functionalized epoxides in the presence of hydroxyl-modified tetraphenylethylene(TPE-OH).TPE-OH was used as chain transfer agent to afford well-defined polycarbonates with controlled molecular weight(6000—17000 g·mol^(–1))and aggregation-induced emission characteristics.Through temperature-dependent fluorescence intensity study,low critical solution transition of TPE-labeled polycarbonates were determined and the fine details of thermal-induced phase transition process were monitored.Further research indicated that temperature-controlled aggregation and dissociation of TPE moieties are the main reason for fluorescence intensity variations.We anticipate that this work could offer a method to visualize the thermal transition process of thermoresponsive polycarbonates and broaden their application fields as smart materials.展开更多
基金supported by grants from the National Key R&D Program of China(2022YFC2703700,2022YFC2703701 to Y.G.and 2022YFC2703700,2022YFC2703703 to G.S.)National Natural Science Foundation of China(31872810,82171851 to Y.G.+3 种基金31970559 to B.J.31970781 to G.S.)Key Research and Development Program of Shandong Province(2016GSF201143 to B.J.)Young Scholars Program of Shandong University(to B.J.)。
文摘Dysregulated lineage commitment of mesenchymal stem cells(MSCs)contributes to impaired bone formation and an imbalance between adipogenesis and osteogenesis during skeletal aging and osteoporosis.The intrinsic cellular mechanism that regulates MSC commitment remains unclear.Here,we identified Cullin 4B(CUL4B)as a critical regulator of MSC commitment.CUL4B is expressed in bone marrow MSCs(BMSCs)and downregulated with aging in mice and humans.Conditional knockout of Cul4b in MSCs resulted in impaired postnatal skeletal development with low bone mass and reduced bone formation.Moreover,depletion of CUL4B in MSCs aggravated bone loss and marrow adipose accumulation during natural aging or after ovariectomy.In addition,CUL4B deficiency in MSCs reduced bone strength.Mechanistically,CUL4B promoted osteogenesis and inhibited adipogenesis of MSCs by repressing KLF4 and C/EBPδexpression,respectively.The CUL4B complex directly bound to Klf4 and Cebpd and epigenetically repressed their transcription.Collectively,this study reveals CUL4B-mediated epigenetic regulation of the osteogenic or adipogenic commitment of MSCs,which has therapeutic implications in osteoporosis.
基金supported by the National Natural Science Foundation of China(No.31970559,82171851,32370652).
文摘It is estimated that infertility impacts 8%-12%of reproductive-aged couples worldwide.Female infertility accounts for 37%of causes among infertile couples,and ovulatory dysfunction is regarded as its most common factor.1 cUL4B belongs to the Cullin family,whose members are the scaffolding proteins of Cullin-RING E3 ligases(CRLs).Human CUL4B gene mutations result in X-linked mental retardation syndromes.In addition to mental retardation,patients have symptoms such as short stature,obesity,and hypogonadism.
基金the financial support from the Fundamental Science Center projector in National Natural Science Foundation of China(Grant No.51988102)Key Research Program of Frontier Sciences,CAS(Grant No.QYZDJ-SSW-JSC017).
文摘Thermoresponsive polymers with simultaneous biodegradability and signal“self-reporting”outputs that meet for advanced applications are hard to obtain.To address this issue,we developed fluorescence signal“self-reporting”biodegradable thermoresponsive polycarbonates through the immortal copolymerization of CO_(2)and oligoethylene glycol monomethyl ether-functionalized epoxides in the presence of hydroxyl-modified tetraphenylethylene(TPE-OH).TPE-OH was used as chain transfer agent to afford well-defined polycarbonates with controlled molecular weight(6000—17000 g·mol^(–1))and aggregation-induced emission characteristics.Through temperature-dependent fluorescence intensity study,low critical solution transition of TPE-labeled polycarbonates were determined and the fine details of thermal-induced phase transition process were monitored.Further research indicated that temperature-controlled aggregation and dissociation of TPE moieties are the main reason for fluorescence intensity variations.We anticipate that this work could offer a method to visualize the thermal transition process of thermoresponsive polycarbonates and broaden their application fields as smart materials.
