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Liu H.,Peking University Shenzhen | Yang H.,Peking University Shenzhen | Zhu D.,Peking University Shenzhen | Sui X.,Peking University Shenzhen | And 19 more authors.
Cell Research | Year: 2014

The applications of human pluripotent stem cell (hPSC)-derived cells in regenerative medicine has encountered a long-standing challenge: how can we efficiently obtain mature cell types from hPSCs? Attempts to address this problem are hindered by the complexity of controlling cell fate commitment and the lack of sufficient developmental knowledge for guiding hPSC differentiation. Here, we developed a systematic strategy to study hPSC differentiation by labeling sequential developmental genes to encompass the major developmental stages, using the directed differentiation of pancreatic β cells from hPSCs as a model. We therefore generated a large panel of pancreas-specific mono-and dual-reporter cell lines. With this unique platform, we visualized the kinetics of the entire differentiation process in real time for the first time by monitoring the expression dynamics of the reporter genes, identified desired cell populations at each differentiation stage and demonstrated the ability to isolate these cell populations for further characterization. We further revealed the expression profiles of isolated NGN3-eGFP + cells by RNA sequencing and identified sushi domain-containing 2 (SUSD2) as a novel surface protein that enriches for pancreatic endocrine progenitors and early endocrine cells both in human embryonic stem cells (hESC)-derived pancreatic cells and in the developing human pancreas. Moreover, we captured a series of cell fate transition events in real time, identified multiple cell subpopulations and unveiled their distinct gene expression profiles, among heterogeneous progenitors for the first time using our dual reporter hESC lines. The exploration of this platform and our new findings will pave the way to obtain mature β cells in vitro. © 2014 IBCB, SIBS, CAS All rights reserved.

Wang C.,CAS Institute of Zoology | Zhang Y.,Academy of Military Medicine Science | Wu B.,CAS Institute of Zoology | Liu S.,U.S. Center for Disease Control and Prevention | And 8 more authors.
PLoS ONE | Year: 2013

The 2009 influenza pandemic had a tremendous social and economic impact. To study the genetic diversity and evolution of the 2009 H1N1 virus, a mutation network for the non-structural (NS) gene of the virus was constructed. Strains of the 2009 H1N1 pandemic influenza A virus could be divided into two categories based on the V123I mutation in the NS1 gene: G1 (characterized as 123 Val) and G2 (characterized as 123 Ile). Sequence homology analysis indicated that one type of NS sequence, primarily isolated from Mexico, was likely the original type in this pandemic. The two genotypes of the virus presented distinctive clustering features in their geographic distributions. These results provide additional insight into the genetics and evolution of human pandemic influenza H1N1. © 2013 Wang et al.

Ma H.,CAS National Center for Nanoscience and Technology | Ning J.,Beijing Institute of Radiation Medicine | Ning J.,Academy of Military Medicine Science | Ning J.,Chinese Peoples Armed Police forces Academy | And 11 more authors.
Biomarkers | Year: 2014

We developed a high-performance ELISA assay and measured serum BHMT levels in healthy individuals and patients with acute liver injury (ALI). The detection range of this ELISA assay was from 1.56 to 100ng/ml. BHMT levels are significantly higher in ALI groups. In the healthy group (n=244), the median value (interquartile range, IQR 0-56.40) was 1.83ng/ml. In the ALI group (n=42), the median value of BHMT was 748.48ng/ml (IQR, 0-51095.92). ROC curve analysis demonstrated good sensitivity (0.86) and specificity (0.98). In addition, in five ALI cases with time course samples available, BHMT and ALT both followed the "rise and fall" temporal pattern with the disease progression. However, the slopes of BHMT curves were steeper than ALT curves. And in three out of the five cases, BHMT levels peaked 1 day earlier than ALT levels be a sensitive marker with good prognostic value. © 2014 Informa UK Ltd. All rights reserved.

Zhou H.,Chinese Institute of Basic Medical Sciences | Guo M.,Academy of Military Medicine Science | Bian C.,Chinese Institute of Basic Medical Sciences | Sun Z.,Chinese Institute of Basic Medical Sciences | And 4 more authors.
Biology of Blood and Marrow Transplantation | Year: 2010

The success of treatment for sclerodermatous chronic graft-versus-host disease (ScGVHD) remains disappointing. The immunomodulatory ability of bone marrow (BM)-derived mesenchymal stem cells (MSCs) shows promise in treating GVHD, especially given its previous success in treating patients with acute GVHD (aGVHD). The potential efficacy and safety issues for treating cGVHD, particularly ScGVHD, remain to be clarified, however. Here, we report 4 patients with ScGVHD who received MSCs expanded ex vivo from unrelated donors by intra-BM injection. After MSC infusion, the ratio of helper T lymphocyte (Th) 1 cells to Th2 cells was dramatically reversed, with an increase in Th1 and a decrease in Th2 achieving a new balance. Correspondingly, symptoms gradually improved in all 4 patients. During the course of MSC treatment, the patients' vital signs and laboratory results remained normal. At the time of this report, none of the 4 patients had experienced recurrence of leukemia. Although this study alone cannot guarantee the application of MSCs in ScGVHD, our findings strongly suggest that this treatment is therapeutically practicable, with no detectable side effects. This approach may provide new insight into the clinical treatment of ScGVHD, with the aim of greatly increasing the survival rate in patients with leukemia who undergo allogeneic BM transplantation (BMT). © 2010 American Society for Blood and Marrow Transplantation.

Gong W.,Jilin University | Gong W.,Academy of Military Medicine Science | Jiang Y.,Academy of Military Medicine Science | Za Y.,Guangdong Center for Animal Disease Control | And 7 more authors.
Virus Research | Year: 2010

Phylogenetic studies have revealed a profound understanding about the biodiversity of rabies viruses in China, but little is known about their evolutionary dynamics in the country. In the present study, the complete G gene sequences of 33 rabies virus isolates (RABVs) isolated from distinct Chinese provinces were determined and phylogenetic analysis was conducted using these G sequences and 93 others retrieved from GenBank representing China and Southeast Asia. Further evolutionary history of RABV was estimated using a Bayesian Markov chain Monte Carlo method to understand the temporal and spatial dynamics of this virus. Results showed that rabies viruses in China and Southeast Asia share a common ancestor and form 2 clades with each being further divided into 3 lineages. The time of the most recent common ancestor of current RABV strains was estimated to be year 1654 (1514-1812) and the viruses circulating in Southeast Asia likely derived from China. © 2010 Elsevier B.V.

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