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Phenotypic changes of Schwann cells on the proximal stump of injured peripheral nerve during repair using small gap conduit tube

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Neural Regeneration Research 2017年第9期12卷 1538-1543页

作者： Shi-jun Zhang Wen-liang Wu Kai-yun Yang Yun-zhen Chen Hai-chun Liu Department of Orthopedics Qilu Hospital of Shandong University Laboratory of Ears Nose and Throat Oral and Maxillofacial Surgery Qilu Hospital of Shandong University

Dedifferentiation of Schwann cells is an important feature of the response to peripheral nerve injury and specific negative myelination reg- ulators are considered to have a major role in this process. However, most experiments have focused on the distal nerve stump, where the notch signaling pathway is strongly associated with Schwann cell dedifferentiation and repair of the nerve. We observed the phenotypic changes of Schwann cells and changes of active notch signaling on the proximal stump during peripheral nerve repair using small gap conduit tubulization. Eighty rats, with right sciatic nerve section of 4 mm, were randomly assigned to conduit bridging group and control group （epineurium suture）. Glial fibrillary acidic protein expression, in myelinating Schwann cells on the proximal stump, began to up-reg- ulate at 1 day after injury and was still evident at 5 days. Compared with the control group, notchl mRNA was expressed at a higher level in the conduit bridging group during the first week on the proximal stump. Hesl mRNA levels in the conduit bridging group significantly increased compared with the control group at 3, 5, 7 and 14 days post-surgery. The change of the notch intracellular domain shared a simi- lar trend as Hesl mRNA expression. Our results confirmed that phenotypic changes of Schwann cells occurred in the proximal stump. The differences in these changes between the conduit tubulization and epineurium suture groups correlate with changes in notch signaling. This suggests that active notch signaling might be a key mechanism during the early stage of neural regeneration in the proximal nerve stump.

关键词： nerve regeneration Schwann cells nerve injury small gap conduit therapy chitin peripheral nerve injury notch signaling notch 1 Hes1 glial fibrillary acidic protein S100 neural regeneration

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Transcriptomic landscape regulated by the 14 types of bone morphogenetic proteins(BMPs)in lineage commitment and differentiation of mesenchymal stem cells(MSCs)

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Genes & Diseases 2019年第3期6卷 258-275页

作者： Linghuan Zhang Qing Luo Yi Shu Zongyue Zeng Bo Huang Yixiao Feng Bo Zhang Xi Wang Yan Lei Zhenyu Ye Ling Zhao Daigui Cao Lijuan Yang Xian Chen Bin Liu William Wagstaff Russell R*Reid Hue H*Luu Rex C*Haydon Michael J*Lee Jennifer Moriatis Wolf Zhou Fu Tong-Chuan He Quan Kang Stem Cell Biology and Therapy Laboratory Ministry of Education Key Laboratory of Child Development and DisordersThe Children’s Hospital of Chongqing Medical UniversityChongqing 400014China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA c Ministry of Education Key Laboratory of Diagnostic Medicine School of Laboratory MedicineChicagoIL 60637USA d The Affiliated Hospitals of Chongqing Medical University Chongqing 400016China e Department of Clinical Laboratory Medicine The Second Affiliated Hospital of Nanchang UniversityNanchang 330006China f Key Laboratory of Orthopaedic Surgery of Gansu Province Departments of Orthopaedic Surgery and Obstetrics and GynecologyThe First and Second Hospitals of Lanzhou UniversityLanzhou 730030China g Department of General Surgery The Second Affiliated Hospital of Soochow UniversitySuzhou 215004China Department of Clinical Laboratory Medicine The Affiliated Hospital of Qingdao UniversityQingdao 266061China Department of Biology School of Life SciencesSouthwest UniversityChongqing 400715China Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Mesenchymal stem cells(MSCs)are ubiquitously-existing multipotent progenitors that can self-renew and differentiate into multiple lineages including osteocytes,chondrocytes,adipocytes,tenocytes and *** represent one of the most commonly-used adult progenitors and serve as excellent progenitor cell models for investigating lineagespecific differentiation regulated by various cellular signaling pathways,such as bone morphogenetic proteins(BMPs).As members of TGFb superfamily,BMPs play diverse and important roles in development and adult *** least 14 BMPs have been identified in *** BMPs exert distinct but overlapping biological *** a comprehensive analysis of 14 BMPs in MSCs,we demonstrated that BMP9 is one of the most potent BMPs in inducing osteogenic differentiation of ***,a global mechanistic view of BMP signaling in regulating the proliferation and differentiation of MSCs remains to be fully ***,we conducted a comprehensive transcriptomic profiling in the MSCs stimulated by 14 types of *** clustering analysis classifies 14 BMPs into three subclusters:an osteo/chondrogenic/adipogenic cluster,a tenogenic cluster,and BMP3 *** also demonstrate that six BMPs(e.g.,BMP2,BMP3,BMP4,BMP7,BMP8,and BMP9)can induce ISmads effectively,while BMP2,BMP3,BMP4,BMP7,and BMP11 up-regulate Smad-independent MAP kinase ***,we show that many BMPs can upregulate the expression of the signal mediators of Wnt,notch and PI3K/AKT/mTOR *** the reported transcriptomic changes need to be further validated,our expression profiling represents the first-of-its-kind to interrogate a comprehensive transcriptomic landscape regulated by the 14 types of BMPs in MSCs.

关键词： Bone morphogenetic proteins(BMPs) MAP kinase signaling Mesenchymal stem cells notch signaling PI3K/AKT/mTOR pathway Smad signaling TGFb superfamily Wnt signaling

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GATA2^(−/−) human ESCs undergo attenuatedendothelial to hematopoietic transition andthereafter granulocyte commitment

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Cell Regeneration 2015年第1期4卷 32-46页

作者： Ke Huang Juan Du Ning Ma Jiajun Liu Pengfei Wu Xiaoya Dong Minghui Meng Wenqian Wang Xin Chen Xi Shi Qianyu Chen Zhongzhou Yang Shubin Chen Jian Zhang Yuhang Li Wei Li Yi Zheng Jinglei Cai Peng Li Xiaofang Sun Jinyong Wang Duanqing Pei Guangjin Pan CAS Key Laboratory of Regenerative Biology South China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine South China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Department of Hematology Sun Yat-sen UniversityGuangzhou 510630China South China University of Technology Guangzhou 510641China Key Laboratory for Major Obstetric Diseases of Guangdong Province GuangzhouChina Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes GuangzhouChina

Background: Hematopoiesis is a progressive process collectively controlled by an elaborate network of transcriptionfactors (TFs). Among these TFs, GATA2 has been implicated to be critical for regulating multiple steps of hematopoiesisin mouse models. However, whether similar function of GATA2 is conserved in human hematopoiesis, especially duringearly embryonic development stage, is largely ***: To examine the role of GATA2 in human background, we generated homozygous GATA2 knockout humanembryonic stem cells (GATA2^(−/−) hESCs) and analyzed their blood differentiation potential. Our results demonstratedthat GATA2^(−/−) hESCs displayed attenuated generation of CD34^(+)CD43^(+) hematopoietic progenitor cells (HPCs), due tothe impairment of endothelial to hematopoietic transition (EHT). Interestingly, GATA2^(−/−) hESCs retained the potentialto generate erythroblasts and macrophages, but never granulocytes. We further identified that SPI1 downregulationwas partially responsible for the defects of GATA2^(−/−) hESCs in generation of CD34^(+)CD43^(+) HPCs and ***, we found that GATA2^(−/−) hESCs restored the granulocyte potential in the presence of notch ***: Our findings revealed the essential roles of GATA2 in EHT and granulocyte development throughregulating SPI1, and uncovered a role of notch signaling in granulocyte generation during hematopoiesis modeled byhuman ESCs.

关键词： hESCs GATA2 EHT HPC Granulocyte notch signaling

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hCLP46 increases Smad3 protein stability via inhibiting its ubiquitin-proteasomal degradation

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Protein & Cell 2015年第10期6卷 767-770页

作者： Yingying Xing Qiaoyun Chu Run Feng Wei Wang Lixin Liu Zhongbing Lu College of Life Sciences University of Chinese Academy of Science Beijing 100049 China Key Laboratory for Polymeric Composite and Functional Materialsof Ministry of Education School of Chemistry and ChemicalEngineering Sun Yat-Sen University Guangzhou 510275 China School of Medical Science Edith Cowan University Joondalup WA 6027 Australia Department of Biochemistry and Molecular Biology Capital Medical University Beijing 10069 China

hCLP46 （human CAP10-1ike protein 46 kDa） was initially isolated and identified from human acute myeloid leukemia transformed from myelodysplastic syndrome （MDS-AML） CD34＋ cells （Teng et al., 2006） and we demons... 详细信息

关键词： Acute Myeloid Leukemia notch signaling DAPT Smad3 Protein Smad3 Expression

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Hidradenitis Suppurativa: An Exploration of Genetic Perturbations and Immune Dysregulation

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International Journal of Dermatology and Venereology 2021年第2期4卷 86-93页

作者： Ana Preda-Naumescu Hana N.Ahmed Tiffany T.Mayo Nabiha Yusuf University of Alabama at Birmingham BirminghamAL 35294USA Department of Dermatology School of MedicineUniversity of Alabama at BirminghamBirminghamAL 35294USA

Hidradenitis suppurativa(HS)is a chronic,inflammatory skin condition that poses a significant diagnostic and therapeutic challenge for clinicians,as the underlying etiology and pathogenesis remains *** host of genetic mutations and immune dysfunction has been identified to be involved in the pathogenesis of HS during recent *** genetic defects,including monogenetic mutations altering subunits ofγ-secretase,a protease that functions through notch signaling to maintain skin appendages,promote epithelial stability,suppress/terminate innate immune responses(ie,Toll-receptors),further have the propensity to induce aberrant cytokine responses that create to a proinflammatory environment,consequently induce hyperkeratosis and promote expression of pro-inflammatory,locally destructive matrix ***-driven inflammation propagates the disease state of HS and contributes to the formation of painful subcutaneous nodules,abscesses,and eventually,fistulas and draining sinus tracts.A closer look at genetic mutations linked to the disease may explain the immune perturbations seen in *** understanding of the immune cells and inflammatory markers expressed in affected individuals provides insight into disease pathogenesis and can help identify therapeutic targets.

关键词： hidradenitis suppurativa genetic perturbations immune dysregulation monogenetic mutations notch signaling cytokine responses

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