Current Location:home > Browse

Submitted Date

Your conditions: Ren, Ruotong(4)

1. chinaXiv:201605.01735 [pdf]

PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype

Duan, Shunlei; Yuan, Guohong; Ren, Ruotong; Xu, Xiuling; Fu, Lina; Li, Ying; Yang, Jiping; Zhang, Weiqi; Liu, Guang-Hui; Liu, Xiaomeng; Li, Jingyi; Tang, Fuchou; Ren, Ruotong; Bai, Ruijun; Liu, Guang-Hui; Ren, Ruotong; Bai, Ruijun; Qu, Jing; Zhang, Weizhou; Wu, Jun
Subjects: Biology >> Biophysics

PTEN is a tumour suppressor frequently mutated in many types of cancers. Here we show that targeted disruption of PTEN leads to neoplastic transformation of human neural stem cells (NSCs), but not mesenchymal stem cells. PTEN-deficient NSCs display neoplasm-associated metabolic and gene expression profiles and generate intracranial tumours in immunodeficientmice. PTEN is localized to the nucleus in NSCs, binds to the PAX7 promoter through association with cAMP responsive element binding protein 1 (CREB)/CREB binding protein (CBP) and inhibits PAX7 transcription. PTEN deficiency leads to the upregulation of PAX7, which in turn promotes oncogenic transformation of NSCs and instates 'aggressiveness' in human glioblastoma stem cells. In a large clinical database, we find increased PAX7 levels in PTEN-deficient glioblastoma. Furthermore, we identify that mitomycin C selectively triggers apoptosis in NSCs with PTEN deficiency. Together, we uncover a potential mechanism of how PTEN safeguards NSCs, and establish a cellular platform to identify factors involved in NSC transformation, potentially permitting personalized treatment of glioblastoma.

submitted time 2016-05-15 Hits1112Downloads469 Comment 0

2. chinaXiv:201605.01529 [pdf]

A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging

Zhang, Weiqi; Wang, Ping; Zhou, Junzhi; Ren, Ruotong; Xu, Xiuling; Yuan, Tingting; Yang, Jiping; Li, Ying; Guan, Dee; Pan, Huize; Duan, Shunlei; Ding, Zhichao; Chen, Chang; Yang, Fuquan; Liu, Guang-Hui; Li, Jingyi; Liu, Xiaomeng; Tang, Fuchou; Suzuki, Keiichiro; Ocampo, Alejandro
Subjects: Biology >> Biophysics

Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1 alpha and nuclear lamina-heterochromatin anchoring protein LAP2 beta. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging.

submitted time 2016-05-12 Hits683Downloads409 Comment 0

3. chinaXiv:201605.01385 [pdf]

CRISPR/Cas9 and TALE: beyond cut and paste

Deng, Liping; Ren, Ruotong; Liu, Guang-Hui; Wu, Jun; Suzuki, Keiichiro; Belmote, Juan Carlos Izpisua; Liu, Guang-Hui; Liu, Guang-Hui
Subjects: Biology >> Biophysics >> Cell Biology

Nuclease-based genome editing has proven to be a powerful and promising tool for disease modeling and gene therapy. Recent advances in CRISPR/Cas and TALE indicate that they could also be used as a targeted regulator of gene expression, as well as being utilized for illuminating specific chromosomal structures or genomic regions.

submitted time 2016-05-12 Hits489Downloads301 Comment 0

4. chinaXiv:201605.00772 [pdf]

Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs

Fu, Lina; Xu, Xiuling; Ren, Ruotong; Zhang, Weiqi; Yang, Jiping; Ren, Xiaoqing; Wang, Si; Zhao, Yang; Liu, Guang-Hui; Ren, Ruotong; Zhang, Weiqi; Liu, Guang-Hui; Qu, Jing; Wu, Jun; Belmonte, Juan Carlos Izpisua; Wu, Jun; Sun, Liang; Yang, Ze; Yu, Yang; Qiao, Jie
Subjects: Biology >> Biophysics >> Cell Biology

Xeroderma pigmentosum (XP) is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patient-specific induced pluripotent stem cells (iPSCs) harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells (NSCs) or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clarify the molecular mechanisms of neurological abnormalities in the XP patients.

submitted time 2016-05-05 Hits482Downloads287 Comment 0

  [1 Pages/ 4 Totals]