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Regulation of neural stem cell by bone morphogenetic protein (BMP) signaling during brain development
Yiming SUN, Zhiheng XU
Front Biol. 2010, 5 (5): 380-385.
https://doi.org/10.1007/s11515-010-0860-5
Neurogenesis is the process in which neurons are generated from neural stem/progenitor cells (NSCs/NPCs). It involves the proliferation and neuronal fate specification/differentiation of NSCs, as well as migration, maturation and functional integration of the neuronal progeny into neuronal network. NSCs exhibit the two essential properties of stem cells: self-renewal and multipotency. Contrary to previous dogma that neurogenesis happens only during development, it is generally accepted now that neurogenesis can take place throughout life in mammalian brains. This raises a new therapeutic potential of applying stem cell therapy for stroke, neurodegenerative diseases and other diseases. However, the maintenance and differentiation of NSCs/NPCs are tightly controlled by the extremely intricate molecular networks. Uncovering the underlying mechanisms that drive the differentiation, migration and maturation of specific neuronal lineages for use in regenerative medicine is, therefore, crucial for the application of stem cell for clinical therapy as well as for providing insight into the mechanisms of human neurogenesis. Here, we focus on the role of bone morphogenetic protein (BMP) signaling in NSCs during mammalian brain development.
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Identification of cancer stem cells: from leukemia to solid cancers
Yinghui HUANG, Xiaoxue QIU, Ji-Long CHEN
Front Biol. 2010, 5 (5): 407-416.
https://doi.org/10.1007/s11515-010-0850-7
Cancer stem cells (CSCs) are widely considered to be a small cell population in leukemia and many solid cancers with the properties including self-renewal and differentiation to non-tumorigenic cancer cells. Identification and isolation of CSCs significantly depend on the special surface markers of CSCs. Aberrant gene expression and signal transduction contribute to malignancies of CSCs, which result in cancer initiation, progression and recurrence. The inefficient therapy of cancers is mainly attributed to the failure of elimination of the malignant CSCs. However, CSCs have not been detected in all cancers and hierarchical organization of tumors might challenge cancer stem cell models. Additionally, opinions about the validity of the CSC hypothesis, the biological properties of CSCs, and the relevance of CSCs to cancer therapy differ widely. In this review, we discuss the debate of cancer stem cell model, the parameters by which CSCs can or cannot be defined, and the advances in the therapy of CSCs.
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Differential effects of recombinant fusion proteins TAT-OCT4 and TAT-NANOG on adult human fibroblasts
Jiani CAO, Zhifeng XIAO, Bing CHEN, Yuan GAO, Chunying SHI, Jinhuan WANG, Jianwu DAI
Front Biol. 2010, 5 (5): 424-430.
https://doi.org/10.1007/s11515-010-0800-4
OCT4 and NANOG are two important transcription factors for maintaining the pluripotency and self-renewal abilities of embryonic stem (ES) cells. Meanwhile they play key roles in the induced pluripotent stem (iPS) cells. In this study, recombinant transcript factors TAT-NANOG and TAT-OCT4, which contained a fused powerful protein transduction domain (PTD) TAT from human immunodeficiency virus (HIV), were produced. Each fusion protein could be transported into human adult fibroblasts (HAF) successfully and activated the endogenous transcription of both nanog and oct4. Our study revealed the inter-regulation and autoregulation abilities of solo oct4 or nanog in the process of iPS cell reprogramming. Meanwhile the transduction of TAT-NANOG could accelerate the growth rate of HAF cells, and the key cell cycle regulator cdc25a was up-regulated. Thus cdc25a may be involved in the regulation of cell growth by NANOG. In addition, the TAT fusion protein technology provided a novel way to improve cell growth that is more controllable and safer.
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Screening for self-renewal factors by a combination of mRNA and CGH microarray in human embryonic stem cells
Lei XIAO, Lixiazi HE, Saul J. SHARKIS
Front Biol. 2010, 5 (5): 431-438.
https://doi.org/10.1007/s11515-010-0900-1
Human embryonic stem cells (hESCs) undergo self-renewal while maintaining pluripotency. However, the molecular mechanism that demonstrates how these cells maintain their undifferentiated state and how they self-renew is poorly understood. Here, we characterized an aneuploidy H1 hESC subline (named H1T) using karyotyping and comparative genomic hybridization (CGH) microarray. Because the H1T hESC line displays a self-renewal advantage while maintaining an undifferentiated state, we speculated that the expression patterns of specific genes which are related to pluripotency or differentiation were altered; therefore, we attempted to screen for molecules that are propitious for maintenance of stemness by performing a combination of mRNA and CGH microarray analysis which compared the aneuploidy H1T hESC subline versus the euploid H1 hESC line. It is discovered that some genes are up-regulated in H1T hESC subline such as TBX2 and Wnt3, while some are downregulated, for example, Fbxo7 and HMG2L1. Our findings should fascilitate the study of the complex signaling network which maintains hESC pluripotency and function.
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Cloning efficiency following ES cell nuclear transfer is influenced by the methylation state of the donor nucleus altered by mutation of DNA methyltransferase 3a and 3b
Xiangpeng DAI, Xiaoyang ZHAO, Hai TANG, Jie HAO, Jean-Paul RENARD, Qi ZHOU, Alice JOUNEAU, Liu WANG
Front Biol. 2010, 5 (5): 439-444.
https://doi.org/10.1007/s11515-010-0840-9
The epigenetic state of donor cells plays a vital role in the nuclear reprogramming and chromatin remodeling of cloned embryos. In this study we investigated the effect of DNA methylation state of donor cells on the development of mouse embryos reconstructed with embryonic stem (ES) cell nuclei. Our results confirmed that deletion of the DNA methyltransferase 3a (Dnmt3a) and DNA methyltransferase 3b (Dnmt3b) distinctly decreases the level of DNA methylation in ES cells. In contrast to wild type ES cells (J1), Dnmt3a-/-3b-/- (DKO) and Dnmt3b-/- (3bKO) donor cells significantly elevated the percentage of embryonic stem cell nuclear transfer (ECNT) morula, blastocysts and postimplantation embryos (P<0.05). However, the efficiency of establishment of NT-ES cell lines derived from DKO reconstructed blastocysts was not improved, and the expression pattern of OCT4 and CDX2 in cloned blastocysts and postimplantation embryos was not altered either. Our results suggest that the DNA methylation state of the donor nucleus is an important factor in regulation of the donor nuclear reprogramming.
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Prostaglandin E2 promotes hematopoietic development from human embryonic stem cells
Chao YANG, Jia-Fei XI, Xiao-Yan XIE, Wen YUE, Ruo-Yong WANG, Qiong WU, Li-Juan HE, Xue NAN, Yan-Hua LI, Xue-Tao PEI
Front Biol. 2010, 5 (5): 445-454.
https://doi.org/10.1007/s11515-010-0810-2
Recent studies have suggested that prostaglandin (PG) E2 (PGE2) and the prostaglandin pathway are essential for hematopoietic stem cell growth and development. However, similar studies on hematopoietic commitment from human embryonic stem cells (hESCs) are still limited. Here we report that the addition of PGE2 promotes hematopoietic differentiation of hESCs. The induced cells from hESCs/OP9 co-culture and in the presence of PGE2 were characterized by reverse transcription-PCR (RT-PCR), flow cytometry, colony-forming assays and Wright-Giemsa staining. Our results demonstrated that PGE2 exposure could alter the gene expression pattern and morphology of co-cultured hESCs and resulted in a robust hematopoietic differentiation with higher frequencies of CD34+ and CD45+ cells. Furthermore, the Smad signaling pathway may be involved in PGE2 and OP9 induced hematopoietic differentiation of hESCs. This research may improve our knowledge of stem cell regulation and hopefully lead to better stem cell-based therapeutic options.
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A versatile tool for tracking the differentiation of human embryonic stem cells
Weiqiang LI, Jie QIN, Xinyu LI, Li ZHANG, Chang LIU, Fei CHEN, Zifei WANG, Lirong ZHANG, Xiuming ZHANG, Bruce T. LAHN, Andy Peng XIANG
Front Biol. 2010, 5 (5): 455-463.
https://doi.org/10.1007/s11515-010-0870-3
The ability of human embryonic stem cells (hESCs) to undergo indefinite self-renewal in vitro and to produce lineages derived from all three embryonic germ layers both in vitro and in vivo makes such cells extremely valuable in both clinical and research settings. However, the generation of specialized cell lineages from a mixture of differentiated hESCs remains technically difficult. Tissue specific promoter-driven reporter genes are powerful tools for tracking cell types of interest in differentiated cell populations. Here, we describe the construction of modular lentivectors containing different tissue-specific promoters (Tα1 of α-tubulin; aP2 of adipocyte Protein 2; and AFP of alpha fetoprotein) driving expression of humanized Renilla green fluorescent protein (hrGFP). To this end, we used MultiSite gateway technology and employed the novel vectors to successfully monitor hESC differentiation. We present a versatile method permitting target cells to be traced. Our system will facilitate research in developmental biology, transplantation, and in vivo stem cell tracking.
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