MicroRNA: A new player in stem cells

Zhang, Baohong; Pan, Xiaoping; Anderson, Todd A.

doi:10.1002/jcp.20713

Cited by 94 publications

(64 citation statements)

References 68 publications

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“…Another component of the miRNA processing machinery, Dicer, is also known to play a critical role in maintaining the proliferating pool of chondrocytes by regulating chondrocyte proliferation and inhibiting premature differentiation of these cells to postmitotic hypertrophic chondrocytes (Kanellopoulou et al, 2005). Mammalian Dicer) ⁄ ) embryos die in the early stages of development and are characterized by defects in cell self-renewal, miRNA maturation, and failure of cells to differentiate into functional organs or tissues (Hatfield et al, 2005;Kanellopoulou et al, 2005;Murchison et al, 2005;Yang et al, 2005;Shcherbata et al, 2006;Zhang et al, 2006;Wang et al, 2007). Dicer binds directly to Ago proteins, and the resulting complex inhibits the RNase activity of Dicer in vitro in a dose-dependent manner.…”

Section: Introductionmentioning

confidence: 99%

“…We also showed that Ago2 initiates signal transfer through ion channel activation, thus playing an important role in the regulation of cytosolic proteins, such as JAK ⁄ STAT3, that phosphorylate specific ATSC-reprogramming signal pathways. MicroRNAs are widespread agents of posttranscriptional silencing and are highly related to stem cell behavior, including cell self-renewal, differentiation, and senescence or aging (Hatfield et al, 2005;Kanellopoulou et al, 2005;Shcherbata et al, 2006;Zhang et al, 2006;Wang et al, 2007). Controlling the balance between selfrenewal and differentiation as well as the ability to transition from growth to differentiation or senescence is crucial to stem cell plasticity.…”

Section: Introductionmentioning

confidence: 99%

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Nuclear Argonaute 2 regulates adipose tissue‐derived stem cell survival through direct control of miR10b and selenoprotein N1 expression

et al. 2011

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SummaryArgonaute 2 (Ago2) has a leading function in miRNAinduced RNA silencing, a conserved gene regulatory mechanism in cells and organisms. miRNAs are critical for stem cell self-renewal, development, and other functions. Here, we report that nuclear Ago2, by binding to a specific region of functional genes, directly controls adipose tissue-derived stem cell (ATSC) survival in response to a critical dose of reactive oxygen species (ROS)-mediated oxidative cell damage or senescence. The role of nuclear Ago2 has not been previously reported. Here, we show that human ATSCs in which Ago2 was downregulated underwent apoptosis. Silencing of Ago2 in ATSCs significantly induces upregulation of miR10b and miR23b expression. These miRNAs directly interfere with ROSscavenging gene expression, such as TXNL1 and GPX3. Upregulation of miR10b and miR23b is sufficient to induce ATSC cell apoptosis via p38 MAPK phosphorylation and caspase 3 activation. In addition, Ago2 overexpression or interference by miR10b and miR23b expression in ATSCs partially rescued H 2 O 2 ⁄ ROS-mediated apoptotic cell death by upregulating the expression of TXNL2, JUNK, caspase-3, and cytochrome C. Nuclear Ago2-mediated miR10b and miR23b downregulation also allows cells to escape senescence, which results in telomerase reverse transcriptase, stemness overexpression, and improved self-renewal and differentiation through Wnt5a ⁄ b-catenin activation. Argonaute 2 expression is critical for stem cells to escape senescence by downregulating miR10b and miR23b. The Ago2-binding gene selenoprotein N1 (SEPN1) was also effectively involved in ATSC survival and self-renewal through ROS-mediated p38 MAPK inactivation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nuclear Argonaute 2 regulates adipose tissue‐derived stem cell survival through direct control of miR10b and selenoprotein N1 expression

et al. 2011

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“…A majority of identified miRNAs are highly evolutionarily conserved among many distantly related species, some from worms to human in animals , and mosses to high flowering eudicots in plants (Axtell and Bartel, 2005;Zhang et al, 2006c), suggesting that miRNAs play a very important role in essential biological processes, including developmental timing (Lee et al, 1993), stem cell differentiation (Houbaviy et al, 2003;Hatfield et al, 2005;Zhang et al, 2006b), signaling transduction (Guo et al, 2005;Karp and Ambros, 2005;Kwon et al, 2005), disease (Labourier et al, 2004;Alvarez-Garcia and Miska, 2005), and cancer (Hayashita et al, 2005;Lu et al, 2005b). Currently, miRNAs have been considered one of the most important regulatory molecules, which regulate gene expression at the posttranscriptional levels by targeting mRNAs for direct cleavage of mRNAs or repression of mRNA translation.…”

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confidence: 99%

MicroRNAs and their regulatory roles in animals and plants

Zhang

Wang

Pan

2006

Journal Cellular Physiology

Self Cite

484

301

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microRNAs (miRNAs) are an abundant class of newly identified endogenous non-protein-coding small RNAs. They exist in animals, plants, and viruses, and play an important role in gene silencing. Translational repression, mRNA cleavage, and mRNA decay initiated by miRNA-directed deadenylation of targeted mRNAs are three mechanisms of miRNA-guided gene regulation at the posttranscriptional levels. Many miRNAs are highly conserved in animals and plants, suggesting that they play an essential function in plants and animals. Lots of investigations indicate that miRNAs are involved in multiple biological processes, including stem cell differentiation, organ development, phase change, signaling, disease, cancer, and response to biotic and abiotic environmental stresses. This review provides a general background and current advance on the discovery, history, biogenesis, genomics, mechanisms, and functions of miRNAs.

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“…Many studies have documented the dramatic changes in global gene expression that accompany stem cell differentiation. The expression levels of more than 100 proteins change greater than twofold during osteoblastic differentiation of MSCs (Zhang et al 2006). Examination of such large numbers of potentially relevant genes and gene products can be daunting.…”

Section: Discussionmentioning

confidence: 99%

Efficient method for generating nuclear fractions from marrow stromal cells

Woodbury¹,

Len

Reynolds³

et al. 2008

Cytotechnology

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Stem cells have received significant attention for their envisioned potential to treat currently unapproachable diseases. No less important is the utility of stem cells to serve as model systems of differentiation. Analyses at the transcriptome, miRNA and proteome levels have yielded valuable insights into events underlying stem cell differentiation. Proteomic analysis is often cumbersome, detecting changes in hundreds of proteins that require subsequent identification and validation. Targeted analysis of nuclear constituents would simplify proteomic studies, focusing efforts on transcription factor abundance and modification. To facilitate such studies, a simple and efficient methodology to isolate pure nuclear fractions from Marrow Stromal Cells (MSCs), a clinically relevant stem cell population, has been developed. The modified protocol greatly enhances cell disruption, yielding free nuclei without attached cell body remnants. Light and electron microscopic analysis of purified nuclei demonstrated that preparations contained predominantly intact nuclei with minimal cytoplasmic contamination. Western analysis revealed an approximately eightfold enrichment of the transcription factor CREB in the isolated nuclei over that in the starting homogenates. This simple method for isolation of highly purified nuclear fractions from stem cell populations will allow rigorous examination of nuclear proteins critical for differentiation.

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MicroRNA: A new player in stem cells

Cited by 94 publications

References 68 publications

Nuclear Argonaute 2 regulates adipose tissue‐derived stem cell survival through direct control of miR10b and selenoprotein N1 expression

Nuclear Argonaute 2 regulates adipose tissue‐derived stem cell survival through direct control of miR10b and selenoprotein N1 expression

MicroRNAs and their regulatory roles in animals and plants

Efficient method for generating nuclear fractions from marrow stromal cells

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