Qilin Xu

Publications (3)10.09 Total impact

• Article: Stepwise differentiation of human adipose derived mesenchymal stem cells towards definitive endoderm and pancreatic progenitor cells by mimicking pancreatic development in vivo.

  Jing Li, Li Zhu, Xuebin Qu, Ruizhu Lin, Lianming Liao, Jing Wang, Shihua Wang, Qilin Xu, Robert Chunhua Zhao
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  ABSTRACT: Pancreatic progenitor (PP) cells are tissue-committed cells which can differentiate into all kinds of pancreatic cells. They are potential candidate for regeneration of pancreatic tissue. However, it is unfeasible to acquire PP cells from pancreatic tissues and expand them in vitro. Generation of PP cells from adipose tissue derived mesenchymal stem cells (AD-MSCs) would provide an unlimited source of PP cells. Here we developed a two-step stepwise protocol which induced AD-MSCs to generate FOXA2- or SOX17-positive definitive endoderm (DE) (5 days) and PDX1-positive PP cells (4-6 days). By mimicking the developmental progress in embryonic development, we optimized the timing and combination of cytokines to activate the key signaling pathways during pancreatic development. We found that activating Nodal/Activin signal with Activin A could induce differentiation of AD-MSCs towards DE, which could be further promoted by Wnt signaling pathway activator Wnt3a. Besides, transient T (BRACHYURY)+ mesendodermal cells were observed during formation of DE from AD-MSCs. Subsequently Wnt signaling pathway inhibitor Dkk1 along with retinoic acid (RA) /FGF2 (60 ng/mL) further induced AD-MSCs-derived DE cells to differentiate into PDX1-positive PP cells. The derived PP cells were capable to form pancreatic endocrine or exocrine cells. In conclusion, we established a stepwise protocol which can derive DE and PP cells from AD-MSCs. It might provide an unlimited source of autologous PP cells for pancreatic diseases.
  Stem cells and development 12/2012; · 4.15 Impact Factor
• Article: Mesenchymal stem cells play a potential role in regulating the establishment and maintenance of epithelial-mesenchymal transition in MCF7 human breast cancer cells by paracrine and induced autocrine TGF-β.

  Qilin Xu, Liang Wang, Hongling Li, Qin Han, Jing Li, Xuebin Qu, Shan Huang, Robert Chunhua Zhao
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  ABSTRACT: Although the epithelial-mesenchymal transition (EMT) is a normal process that occurs during development, it is thought to be associated with cancer progression and metastasis. Emerging evidence links mesenchymal stem cells (MSCs) in the tumor microenvironment with the occurrence of EMT in cancer progression. In this study, the human breast cancer cell line MCF7 was co-cultured with human adipose-derived MSCs (hAD-MSCs) in a transwell system. Co-cultured cells were analyzed for changes in cellular morphology, EMT markers, protein expression and tumor characteristics. We found that co-cultured MCF7 cells underwent EMT and established a stable mesenchymal phenotype after prolonged co-culturing. Here, we demonstrate that paracrine transforming growth factor-β1 (TGF-β1) secreted by hAD-MSCs regulated the establishment of EMT in MCF7 cells by targeting the ZEB/miR-200 regulatory loop. The downregulation of paracrine TGF-β1 levels can inhibit and reverse the EMT progress by downregulating ZEB1/2 and upregulating miR-200b and miR-200c. The maintenance of a stable mesenchymal state by MCF7 cells required the establishment of autocrine TGF-β signaling to drive and sustain ZEB expression, which had been initiated by the prolonged co-culturing with hAD-MSCs. These results suggest that MSCs may promote breast cancer metastasis by stimulating and facilitating the EMT process.
  International Journal of Oncology 07/2012; 41(3):959-68. · 2.40 Impact Factor
• Article: MicroRNA-100 regulates osteogenic differentiation of human adipose-derived mesenchymal stem cells by targeting BMPR2.

  Yang Zeng, Xuebin Qu, Hongling Li, Shan Huang, Shihua Wang, Qilin Xu, Ruizhu Lin, Qin Han, Jing Li, Robert Chunhua Zhao
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  ABSTRACT: Elucidation of the molecular mechanisms governing human adipose-derived mesenchymal stem cells (hASCs) osteogenic differentiation is of great importance for improving the treatment of bone-related diseases. In this study, we examined the role of microRNA (miR)-100 on the osteogenesis of hASCs. Overexpression of miR-100 inhibited osteogenic differentiation of hASCs in vitro, whereas downregulation of miR-100 enhanced the process. Target prediction analysis and dual luciferase report assay confirmed that bone morphogenetic protein receptor type II (BMPR2) was a direct target of miR-100. Furthermore, knockdown of BMPR2 by RNA interference inhibited osteogenic differentiation of hASCs, similar as the effect of upregulation miR-100. Taken together, our findings imply that miR-100 plays a negative role in osteogenic differentiation and might act through targeting BMPR2.
  FEBS letters 06/2012; 586(16):2375-81. · 3.54 Impact Factor