共查询到20条相似文献,搜索用时 31 毫秒
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Metazoan growth and development is maintained by populations of undifferentiated cells, commonly known as stem cells. Stem cells possess several characteristic properties, including dividing through self-renewing divisions and generating progeny that differentiate to have specialized cell fates. Multiple signaling pathways have been identified which coordinate stem cell proliferation with maintenance and differentiation. Relatively recently, the small, non-protein coding microRNAs (miRNAs) have been identified to function as important regulators in stem cell development. Individual miRNAs are capable of directing the translational repression of many mRNAs targets, generating widespread changes in gene expression. In addition, dysfunction of miRNA expression is commonly associated with cancer development. Cancer stem cells, which are likely responsible for initiating and maintaining tumorigenesis, share many similarities with stem cells and some mechanisms of miRNA function may be in common between these two cell types.Key words: stem cell, miRNA, mammalian, neuroblast, pluripotency, cancer, ESC, self-renewal 相似文献
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MicroRNAs (miRNAs) are a newly discovered, yet powerful mechanism for regulating protein expression via mRNA translational inhibition. Loss of all miRNA function within mice leads to embryonic lethality with a loss of the stem cell population in the epiblast and failure to form a primitive streak. These data suggest that miRNAs play a major role in embryonic development. As critical regulation of protein expression is also important for controlling the balance between self-renewal and differentiation in stem cells, the study of miRNAs within this model system is rapidly expanding. New data suggest that stem cells have discrete miRNA expression profiles, which may account for, or contribute to, the intrinsic stem cell properties of self-renewal and pluripotency. Specifically, miRNAs have been implicated in downregulation of cell cycle checkpoint proteins during germ stem cell division. Other data demonstrate that changes in miRNA expression can promote or inhibit stem or progenitor cell differentiation within different cell lineages, including hematopoietic cells, cardiomyocytes, myoblasts, and neural cells. In this review we detail the established functional roles of miRNAs in the embryonic and adult stem cell model systems. Finally, we explore new techniques that exploit endogenous miRNA processing and function for applications in basic and clinical research. 相似文献
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Tian QN Bao ZX Lu P Qin YF Chen SJ Liang F Mai J Zhao JM Zhu ZY Zhang YZ Zhang ST 《Molecular biology reports》2012,39(3):2653-2658
MicroRNAs (miRNAs) are ~22-nt small non-coding RNAs that regulate the expression of specific target genes in many eukaryotes. miRNAs have been shown to play important roles in stem cell maintenance, cell fate determination, and differentiation. Planarians are capable of regenerating entire body plans from tiny fragments; this regenerative capacity is facilitated by a population of pluripotent stem cells known as neoblasts. Planarians have been a classic model system for the study of many aspects of stem cell biology. However, very limited knowledge on miRNA involved in this regulatory mechanism exists. This study profiles the expression of miRNAs in the normal and regenerative tissues of planarians using miRCURY LNA array technology. Thirteen miRNAs showed significant differences in expression between these two tissues. To further confirm our results, we examined the expression of two miRNAs by qRT-PCR. Results show that some known miRNAs may play key roles in the regulatory mechanisms of regeneration. Our findings can be utilized in future research on miRNA function. 相似文献
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Minal Garg 《World journal of stem cells》2012,4(7):62-70
This review discusses the various regulatory charac-teristics of microRNAs that are capable of generating widespread changes in gene expression via post translational repression of many mRNA targets and control self-renewal, differentiation and division of cells. It controls the stem cell functions by controlling a wide range of pathological and physiological processes, including development, differentiation, cellular proliferation, programmed cell death, oncogenesis and metastasis. Through either mRNA cleavage or translational repression, miRNAs alter the expression of their cognate target genes; thereby modulating cellular pathways that affect the normal functions of stem cells, turning them into cancer stem cells, a likely cause of relapse in cancer patients. This present review further emphasizes the recent discoveries on the functional analysis of miRNAs in cancer metastasis and implications on miRNA based therapy using miRNA replacement or anti-miRNA technologies in specific cancer stem cells that are required to establish their efficacy in controlling tumorigenic potential and safe therapeutics. 相似文献
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Sunil K. Mallanna 《Developmental biology》2010,344(1):16-25
MicroRNAs (miRNAs) have emerged as critical regulators of gene expression. These small, non-coding RNAs are believed to regulate more than a third of all protein coding genes, and they have been implicated in the control of virtually all biological processes, including the biology of stem cells. The essential roles of miRNAs in the control of pluripotent stem cells were clearly established by the finding that embryonic stem (ES) cells lacking proteins required for miRNA biogenesis exhibit defects in proliferation and differentiation. Subsequently, the function of numerous miRNAs has been shown to control the fate of ES cells and to directly influence critical gene regulatory networks controlled by pluripotency factors Sox2, Oct4, and Nanog. Moreover, a growing list of tissue-specific miRNAs, which are silenced or not processed fully in ES cells, has been found to promote differentiation upon their expression and proper processing. The importance of miRNAs for ES cells is further indicated by the exciting discovery that specific miRNA mimics or miRNA inhibitors promote the reprogramming of somatic cells into induced pluripotent stem (iPS) cells. Although some progress has been made during the past two years in our understanding of the contribution of specific miRNAs during reprogramming, further progress is needed since it is highly likely that miRNAs play even wider roles in the generation of iPS cells than currently appreciated. This review examines recent developments related to the roles of miRNAs in the biology of pluripotent stem cells. In addition, we posit that more than a dozen additional miRNAs are excellent candidates for influencing the generation of iPS cells as well as for providing new insights into the process of reprogramming. 相似文献
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MicroRNAs (miRNAs) are approximately 22-nt RNA molecules that typically bind to the 3' untranslated regions of target mRNAs and function to either induce mRNA degradation or repress translation. miRNAs have been shown to play important roles in the function of stem cells and cell lineage decisions in a variety of organisms, including humans. Planarians are bilaterally symmetric metazoans that have the unique ability to completely regenerate lost tissues or organs. This regenerative capacity is facilitated by a population of stem cells known as neoblasts. Planarians are therefore an excellent model system for studying many aspects of stem cell biology. Here we report the cloning and initial characterization of 71 miRNAs from the planarian Schmidtea mediterranea. While several of the S. mediterranea miRNAs are members of miRNA families identified in other species, we also identified a number of planarian-specific miRNAs. This work lays the foundation for functional studies aimed at addressing the role of these miRNAs in regeneration, cell lineage decisions, and basic stem cell biology. 相似文献
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Jouneau A Ciaudo C Sismeiro O Brochard V Jouneau L Vandormael-Pournin S Coppée JY Zhou Q Heard E Antoniewski C Cohen-Tannoudji M 《RNA (New York, N.Y.)》2012,18(2):253-264
Over the last years, the microRNA (miRNA) pathway has emerged as a key component of the regulatory network of pluripotency. Although clearly distinct states of pluripotency have been described in vivo and ex vivo, differences in miRNA expression profiles associated with the developmental modulation of pluripotency have not been extensively studied so far. Here, we performed deep sequencing to profile miRNA expression in naive (embryonic stem cell [ESC]) and primed (epiblast stem cell [EpiSC]) pluripotent stem cells derived from mouse embryos of identical genetic background. We developed a graphical representation method allowing the rapid identification of miRNAs with an atypical profile including mirtrons, a small nucleolar RNA (snoRNA)-derived miRNA, and miRNAs whose biogenesis may differ between ESC and EpiSC. Comparison of mature miRNA profiles revealed that ESCs and EpiSCs exhibit very different miRNA signatures with one third of miRNAs being differentially expressed between the two cell types. Notably, differential expression of several clusters, including miR290-295, miR17-92, miR302/367, and a large repetitive cluster on chromosome 2, was observed. Our analysis also showed that differentiation priming of EpiSC compared to ESC is evidenced by changes in miRNA expression. These dynamic changes in miRNAs signature are likely to reflect both redundant and specific roles of miRNAs in the fine-tuning of pluripotency during development. 相似文献
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Spheroids from adipose‐derived stem cells exhibit an miRNA profile of highly undifferentiated cells
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A. Barbara Di Stefano PhD Federica Grisafi MSc Marta Castiglia PhD Alessandro Perez PhD Luigi Montesano MD Alessandro Gulino PhD Francesca Toia MD Daniele Fanale PhD Antonio Russo MD Francesco Moschella MD Angelo A. Leto Barone MD Adriana Cordova MD 《Journal of cellular physiology》2018,233(11):8778-8789
Two‐dimensional (2D) cell cultures have been extensively used to investigate stem cell biology, but new insights show that the 2D model may not properly represent the potential of the tissue of origin. Conversely, three‐dimensional cultures exhibit protein expression patterns and intercellular junctions that are more representative of their in vivo condition. Multiclonal cells that grow in suspension are defined as “spheroids,” and we have previously demonstrated that spheroids from adipose‐derived stem cells (S‐ASCs) displayed enhanced regenerative capability. With the current study, we further characterized S‐ASCs to further understand the molecular mechanisms underlying their stemness properties. Recent studies have shown that microRNAs (miRNAs) are involved in many cellular mechanisms, including stemness maintenance and proliferation, and adipose stem cell differentiation. Most studies have been conducted to identify a specific miRNA profile on adherent adipose stem cells, although little is still known about S‐ASCs. In this study, we investigate for the first time the miRNA expression pattern in S‐ASCs compared to that of ASCs, demonstrating that cell lines cultured in suspension show a typical miRNA expression profile that is closer to the one reported in induced pluripotent stem cells. Moreover, we have analyzed miRNAs that are specifically involved in two distinct moments of each differentiation, namely early and late stages of osteogenic, adipogenic, and chondrogenic lineages during long‐term in vitro culture. The data reported in the current study suggest that S‐ASCs have superior stemness features than the ASCs and they represent the true upstream stem cell fraction present in adipose tissue, relegating their adherent counterparts. 相似文献
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Worldwide obesity is a growing health problem, associated with increased risk of chronic disease. Understanding the molecular basis of adipogenesis and fat cell development in obesity is essential to identify new biomarkers and therapeutic targets for the development of anti-obesity drugs. microRNAs (miRNAs) appear to play regulatory roles in many biological processes associated with obesity, including adipocyte differentiation, insulin action and fat metabolism. Recent studies show miRNAs are dysregulated in obese adipose tissue. During adipogenesis miRNAs can accelerate or inhibit adipocyte differentiation and hence regulate fat cell development. In addition miRNAs may regulate adipogenic lineage commitment in multipotent stem cells and hence govern fat cell numbers. Recent findings suggest miR-519d may be associated with human obesity, but larger case-control studies are needed. Few miRNA targets have been experimentally validated in adipocytes but interestingly both miR-27 and miR-519d target PPAR family members, which are well established regulators of fat cell development. In this review recent advances in our understanding of the role of miRNAs in fat cell development and obesity are discussed. The potential of miRNA based therapeutics targeting obesity is highlighted as well as recommendations for future research which could lead to a breakthrough in the treatment of obesity. 相似文献
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MicroRNAs (miRNAs) are 22 nt non-coding RNAs that regulate expression of downstream targets by messenger RNA (mRNA) destabilization and translational inhibition. A large number of eukaryotic mRNAs are targeted by miRNAs, with many individual mRNAs being targeted by multiple miRNAs. Further, a single miRNA can target hundreds of mRNAs, making these small RNAs powerful regulators of cell fate decisions. Such regulation by miRNAs has been observed in the maintenance of the embryonic stem cell (ESC) cell cycle and during ESC differentiation. MiRNAs can also promote the dedifferentiation of somatic cells to induced pluripotent stem cells. During this process they target multiple downstream genes, which represent important nodes of key cellular processes. Here, we review these findings and discuss how miRNAs may be used as tools to discover novel pathways that are involved in cell fate transitions using dedifferentiation of somatic cells to induced pluripotent stem cells as a case study. 相似文献
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Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells 总被引:1,自引:0,他引:1
Marson A Levine SS Cole MF Frampton GM Brambrink T Johnstone S Guenther MG Johnston WK Wernig M Newman J Calabrese JM Dennis LM Volkert TL Gupta S Love J Hannett N Sharp PA Bartel DP Jaenisch R Young RA 《Cell》2008,134(3):521-533
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miR-21: a small multi-faceted RNA 总被引:1,自引:0,他引:1
More than 1000 microRNAs (miRNAs) are expressed in human cells, some tissue or cell type specific, others considered as house-keeping molecules. Functions and direct mRNA targets for some miRNAs have been relatively well studied over the last years. Every miRNA potentially regulates the expression of numerous protein-coding genes (tens to hundreds), but it has become increasingly clear that not all miRNAs are equally important; diverse high-throughput screenings of various systems have identified a limited number of key functional miRNAs over and over again. Particular miRNAs emerge as principal regulators that control major cell functions in various physiological and pathophysiological settings. Since its identification 3 years ago as the miRNA most commonly and strongly up-regulated in human brain tumour glioblastoma [ 1 ], miR-21 has attracted the attention of researchers in various fields, such as development, oncology, stem cell biology and aging, becoming one of the most studied miRNAs, along with let-7, miR-17–92 cluster ('oncomir-1'), miR-155 and a few others. However, an miR-21 knockout mouse has not yet been generated, and the data about miR-21 functions in normal cells are still very limited. In this review, we summarise the current knowledge of miR-21 functions in human disease, with an emphasis on its regulation, oncogenic role, targets in human cancers, potential as a disease biomarker and novel therapeutic target in oncology. 相似文献
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Monzo M Navarro A Bandres E Artells R Moreno I Gel B Ibeas R Moreno J Martinez F Diaz T Martinez A Balagué O Garcia-Foncillas J 《Cell research》2008,18(8):823-833
MicroRNAs (miRNAs) are essential for regulating cell differentiation and maintaining the pluripotent state of stem cells. Although dysregulation of specific miRNAs has been associated with certain types of cancer, to date no evidence has linked miRNA expression in embryonic and tumor tissues. We assessed the expression of mature miRNAs in human embryonic colon tissue, and in colorectal cancer and paired normal colon tissue. Overlapping miRNA expression was detected between embryonic colonic mucosa and colorectal cancer. We have found that the miR-17-92 cluster and its target, E2F1, exhibit a similar pattern of expression in human colon development and colonic carcinogenesis, regulating cell proliferation in both cases. In situ hybridization confirmed the high level of expression of miR-17-5p in the crypt progenitor compartment. We conclude that miRNA pathways play a major role in both embryonic development and neoplastic transformation of the colonic epithelium. 相似文献
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MicroRNAs (miRNAs) are potent negative regulators of gene expression that have been implicated in most major cellular processes. Despite rapid advances in our understanding of miRNA biogenesis and mechanism, many fundamental questions still remain regarding miRNA function and their influence on cell cycle control. Considering recent reports on the impact of cell-to-cell fluctuations in gene expression on phenotypic diversity, it is likely that looking at the average miRNA expression of cell populations could result in the loss of important information connecting miRNA expression and cell function. Currently, however, there are no efficient techniques to quantify miRNA expression at the single-cell level. Here, a method is described for the detection of individual miRNA molecules in cancer cells using fluorescence in situ hybridization. The method combines the unique recognition properties of locked nucleic acid probes with enzyme-labeled fluorescence. Using this approach, individual miRNAs are identified as bright, photostable fluorescent spots. In this study, miR-15a was quantified in MDA-MB-231 and HeLa cells, while miR-155 was quantified in MCF-7 cells. The dynamic range was found to span over three orders of magnitude and the average miRNA copy number per cell was within 17.5% of measurements acquired by quantitative RT-PCR. 相似文献