2012 Vol. 3, No. 4

News and views
Non-viral iPSCs: a safe way for therapy?
Weiqi Zhang, Di Guan, Jing Qu, Weizhou Zhang, Guang-Hui Liu
2012, 3(4): 241-245. doi: 10.1007/s13238-012-2804-0
Human induced pluripotent stem cells derived hepatocytes: rising promise for disease modeling, drug development and cell therapy
Fei Yi, Guang-Hui Liu, Juan Carlos Izpisua Belmonte
2012, 3(4): 246-250. doi: 10.1007/s13238-012-2918-4
Recent advances in the study of human hepatocytes derived from induced pluripotent stem cells (iPSC) represent new promises for liver disease study and drug discovery. Human hepatocytes or hepatocyte-like cells differentiated from iPSC recapitulate many functional properties of primary human hepatocytes and have been demonstrated as a powerful and efficient tool to model human liver metabolic diseases and facilitate drug development process. In this review, we summarize the recent progress in this field and discuss the future perspective of the application of human iPSC derived hepatocytes.
Neural stem cells: mechanisms and modeling
Jun Yao, Yangling Mu, Fred H. Gage
2012, 3(4): 251-261. doi: 10.1007/s13238-012-2033-6
In the adult brain, neural stem cells have been found in two major niches:the hippocampus and the olfactory bulb. Neurons derived from these stem cells contribute to learning, memory, and the autonomous repair of the brain under pathological conditions. Hence, the physiology of adult neural stem cells has become a significant component of research on synaptic plasticity and neuronal disorders. In addition, the recently developed induced pluripotent stem cell technique provides a powerful tool for researchers engaged in the pathological and pharmacological study of neuronal disorders. In this review, we briefly summarize the research progress in neural stem cells in the adult brain and in the neuropathological application of the induced pluripotent stem cell technique.
Neuronal stem cells in the central nervous system and in human diseases
Qian Wu, Xiaoqun Wang
2012, 3(4): 262-270. doi: 10.1007/s13238-012-2930-8
The process of cortical expansion in the central nervous system is a key step of mammalian brain development to ensure its physiological function. Radial glial (RG) cells are a glial cell type contributing to this progress as intermediate neural progenitor cells responsible for an increase in the number of cortical neurons. In this review, we discuss the current understanding of RG cells during neurogenesis and provide further information on the mechanisms of neurodevelopmental diseases and stem cell-related brain tumorigenesis. Knowledge of neuronal stem cell and relative diseases will bridge benchmark research through translational studies to clinical therapeutic treatments of these diseases.
The genomic stability of induced pluripotent stem cells
Zhao Chen, Tongbiao Zhao
2012, 3(4): 271-277. doi: 10.1007/s13238-012-2922-8
With their capability to undergo unlimited self-renewal and to differentiate into all cell types in the body, induced pluripotent stem cells (iPSCs), reprogrammed from somatic cells of human patients with defined factors, hold promise for regenerative medicine because they can provide a renewable source of autologous cells for cell therapy without the concern for immune rejection. In addition, iPSCs provide a unique opportunity to model human diseases with complex genetic traits, and a panel of human diseases have been successfully modeled in vitro by patient-specific iPSCs. Despite these progresses, recent studies have raised the concern for genetic and epigenetic abnormalities of iPSCs that could contribute to the immunogenicity of some cells differentiated from iPSCs. The oncogenic potential of iPSCs is further underscored by the findings that the critical tumor suppressor p53, known as the guardian of the genome, suppresses induced pluripotency. Therefore, the clinic application of iPSCs will require the optimization of the reprogramming technology to minimize the genetic and epigenetic abnormalities associated with induced pluripotency.
Epigenetic control on cell fate choice in neural stem cells
Xiao-Ling Hu, Yuping Wang, Qin Shen
2012, 3(4): 278-290. doi: 10.1007/s13238-012-2916-6
Derived from neural stem cells (NSCs) and progenitor cells originated from the neuroectoderm, the nervous system presents an unprecedented degree of cellular diversity, interwoven to ensure correct connections for propagating information and responding to environmental cues. NSCs and progenitor cells must integrate cell-intrinsic programs and environmental cues to achieve production of appropriate types of neurons and glia at appropriate times and places during development. These developmental dynamics are reflected in changes in gene expression, which is regulated by transcription factors and at the epigenetic level. From early commitment of neural lineage to functional plasticity in terminal differentiated neurons, epigenetic regulation is involved in every step of neural development. Here we focus on the recent advance in our understanding of epigenetic regulation on orderly generation of diverse neural cell types in the mammalian nervous system, an important aspect of neural development and regenerative medicine.
The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation
Huan Liu, Dandan Jiang, Fangtao Chi, Bin Zhao
2012, 3(4): 291-304. doi: 10.1007/s13238-012-2919-3
Stem cells and progenitor cells are the cells of origin for multi-cellular organisms and organs. They play key roles during development and their dysregulation gives rise to human diseases such as cancer. The recent development of induced pluripotent stem cell (iPSC) technology which converts somatic cells to stem-like cells holds great promise for regenerative medicine. Nevertheless, the understanding of proliferation, differentiation, and self-renewal of stem cells and organ-specific progenitor cells is far from clear. Recently, the Hippo pathway was demonstrated to play important roles in these processes. The Hippo pathway is a newly established signaling pathway with critical functions in limiting organ size and suppressing tumorigenesis. This pathway was first found to inhibit cell proliferation and promote apoptosis, therefore regulating cell number and organ size in both Drosophila and mammals. However, in several organs, disturbance of the pathway leads to specific expansion of the progenitor cell compartment and manipulation of the pathway in embryonic stem cells strongly affects their self-renewal and differentiation. In this review, we summarize current observations on roles of the Hippo pathway in different types of stem cells and discuss how these findings changed our view on the Hippo pathway in organ development and tumorigenesis.
Hippo pathway in intestinal homeostasis and tumorigenesis
Lanfen Chen, Funiu Qin, Xianming Deng, Joseph Avruch, Dawang Zhou
2012, 3(4): 305-310. doi: 10.1007/s13238-012-2913-9
The Hippo pathway plays a crucial role in controlling organ size by inhibiting cell proliferation and promoting cell death. Recent findings implicate that this pathway is involved in the process of intestinal regeneration and tumorigenesis. Here we summarize current studies for the function of the Hippo signaling pathway in intestinal homeostasis, regeneration and tumorigenesis, and the crosstalk between the Hippo signaling pathway and other major signaling pathways, i.e. Wnt, Notch and Jak/Stat signaling pathways in intestinal compartment.
Research article
Bisindoylmaleimide I enhances osteogenic differentiation
Fangfang Zhou, Huizhe Huang, Long Zhang
2012, 3(4): 311-320. doi: 10.1007/s13238-012-2027-4
The Wnt/β-catenin and bone morphogenetic proteins (BMPs) pathways play important roles in controlling osteogenesis. Using a cell-based kinase inhibitor screening assay, we identified the compound bisindoylmaleimide I (BIM) as a potent agonist of the cytosolic β-catenin accumulation in preosteoblast cells. Through suppressing glycogen synthase kinase 3β enzyme activities, BIM upregulated β-catenin responsive transcription and extended duration of BMP initiated signal. Functional analysis revealed that BIM promoted osteoblast differentiation and bone formation. The treatment of human mesenchymal stem cells with BIM promoted osteoblastogenesis. Our findings provide a new strategy to regulate mesenchymal stem cell differentiation by integration of the cellular signaling pathways.