MicroRNA Expression Pattern of Undifferentiated and Differentiated Human Embryonic Stem Cells

Lakshmipathy, Uma; Love, Brad; Goff, Loyal A.; Jörnsten, Rebecka; Graichen, Ralph; Hart, Ronald P.; Chesnut, Jonathan D.

doi:10.1089/scd.2007.0026

Cited by 179 publications

(144 citation statements)

References 68 publications

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“…Previously, miRNA expression has been examined in murine and human ES cells using cloning, microarray, quantitative polymerase chain reaction (PCR), and deep sequencing technologies on selected cell lines [20][21][22][23][24][25][26][27][28][29]. These studies typically involve embryoid body (EB) formation as an intermediate step, and the differentiation protocols extend for several weeks.…”

Section: Establishment Of Induced Pluripotent Stem (Ips) Cell Linesmentioning

confidence: 99%

Characterization of microRNAs Involved in Embryonic Stem Cell States

Stadler

Ivanovska²,

Mehta

et al. 2010

Stem Cells and Development

154

167

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Studies of embryonic stem cells (ESCs) reveal that these cell lines can be derived from differing stages of embryonic development. We analyzed common changes in the expression of microRNAs (miRNAs) and mRNAs in 9 different human ESC (hESC) lines during early commitment and further examined the expression of key ESCenriched miRNAs in earlier developmental states in several species. We show that several previously defi ned hESC-enriched miRNA groups (the miR-302, -17, and -515 families, and the miR-371-373 cluster) and several other hESC-enriched miRNAs are down-regulated rapidly in response to differentiation. We further found that mRNAs up-regulated upon differentiation are enriched in potential target sites for these hESC-enriched miRNAs. Interestingly, we also observed that the expression of ESC-enriched miRNAs bearing identical seed sequences changed dynamically while the cells transitioned through early embryonic states. In human and monkey ESCs, as well as human-induced pluripotent stem cells (iPSCs), the miR-371-373 cluster was consistently up-regulated, while the miR-302 family was mildly down-regulated when the cells were chemically treated to regress to an earlier developmental state. Similarly, miR-302b, but not mmu-miR-295, was expressed at higher levels in murine epiblast stem cells (mEpiSC) as compared with an earlier developmental state, mouse ESCs. These results raise the possibility that the relative expression of related miRNAs might serve as diagnostic indicators in defi ning the developmental state of embryonic cells and other stem cell lines, such as iPSCs. These data also raise the possibility that miRNAs bearing identical seed sequences could have specifi c functions during separable stages of early embryonic development.

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Section: Establishment Of Induced Pluripotent Stem (Ips) Cell Linesmentioning

confidence: 99%

Characterization of microRNAs Involved in Embryonic Stem Cell States

Stadler

Ivanovska²,

Mehta

et al. 2010

Stem Cells and Development

154

167

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“…Furthermore, as these cells differentiate, the microRNA profiles change significantly. Combining the profiling of microRNAs and mRNAs, correlation of gene and microRNA expression predicts regulatory interaction of microRNA and mRNAs involved in both maintenance of pluripotency and differentiation [145]. Based on this, microRNA expression pattern in human embryonic stem cells is included in the panel of tests suggested for qualification of human embryonic stem cells [146].…”

Section: Micrornas In Embryonic and Adult Stem Cellsmentioning

confidence: 99%

“…Using Northern blot analysis, cloning, or array methods, a set of microRNAs specific to pluripotent cell types, such as mouse ES cells [35], mouse or human embryonic carcinoma cells [22], or human ESC [32,[143][144][145], has been identified. Although these studies could not yet ascribe regulatory functions to these microRNA populations, the unique presence of these populations in stem cells and their disappearance during differentiation suggest roles in maintaining "stemness" by suppressing pluripotency and/or restricting cell differentiation.…”

Section: Micrornas In Embryonic and Adult Stem Cellsmentioning

confidence: 99%

“…There are fewer known examples for bone and connective tissue differentiation, but we should expect to find target pathways as these microRNAs are described. Recently, using a concept similar to the "biclustering" of gene expression data [152], we carried out correlation of an mRNA to each microRNA expression level in multiple hESC lines and their differentiated samples organized as separate groups [145]. A similar approach was also used to study the changes in microRNA expression during murine embryonic stem cell differentiation [32].…”

Section: Predicted Microrna-target Interactionsmentioning

confidence: 99%

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Concise Review: MicroRNA Expression in Multipotent Mesenchymal Stromal Cells

Lakshmipathy¹,

Hart

2007

Stem Cells

Self Cite

117

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Mesenchymal stem cells, or multipotent mesenchymal stromal cells (MSC), isolated from various adult tissue sources have the capacities to self-renew and to differentiate into multiple lineages. Both of these processes are tightly regulated by genetic and epigenetic mechanisms. Emerging evidence indicates that the class of single-stranded noncoding RNAs known as microRNAs also plays a critical role in this process. First described in nematodes and plants, microRNAs have been shown to modulate major regulatory mechanisms in eukaryotic cells involved in a broad array of cellular functions. Studies with various types of embryonic as well as adult stem cells indicate an intricate network of microRNAs regulating key transcription factors and other genes, which in turn determine cell fate. In addition, expression of unique microRNAs in specific cell types serves as a useful diagnostic marker to define a particular cell type. MicroRNAs are also found to be regulated by extracellular signaling pathways that are important for differentiation into specific tissues, suggesting that they play a role in specifying tissue identity. In this review, we describe the importance of microRNAs in stem cells, focusing on our current understanding of microRNAs in MSC and their derivatives.

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“…MicroRNAs (miRNAs) are trans-acting regulatory RNAs that act by regulating the translation or directing the degradation of specific mRNA targets and are known to play central roles in many aspects of development, including ES cell pluripotency (Houbaviy et al 2003;Lakshmipathy et al 2007), hematopoiesis (Garzon et al 2006), CNS development (Schratt et al 2006), and embryogenesis (Wienholds et al 2005;Zhao et al 2005;Mineno et al 2006). Other, less well characterized classes of ncRNAs are also implicated in developmental regulation and disease in vertebrates (Mattick and Makunin 2005).…”

mentioning

confidence: 99%

Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation

Dinger¹,

Amaral²,

Mercer³

et al. 2008

Genome Res.

701

588

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The transcriptional networks that regulate embryonic stem (ES) cell pluripotency and lineage specification are the subject of considerable attention. To date such studies have focused almost exclusively on protein-coding transcripts. However, recent transcriptome analyses show that the mammalian genome contains thousands of long noncoding RNAs (ncRNAs), many of which appear to be expressed in a developmentally regulated manner. The functions of these remain untested. To identify ncRNAs involved in ES cell biology, we used a custom-designed microarray to examine the expression profiles of mouse ES cells differentiating as embryoid bodies (EBs) over a 16-d time course. We identified 945 ncRNAs expressed during EB differentiation, of which 174 were differentially expressed, many correlating with pluripotency or specific differentiation events. Candidate ncRNAs were identified for further characterization by an integrated examination of expression profiles, genomic context, chromatin state, and promoter analysis. Many ncRNAs showed coordinated expression with genomically associated developmental genes, such as Dlx1, Dlx4, Gata6, and Ecsit. We examined two novel developmentally regulated ncRNAs, Evx1as and Hoxb5/6as, which are derived from homeotic loci and share similar expression patterns and localization in mouse embryos with their associated protein-coding genes. Using chromatin immunoprecipitation, we provide evidence that both ncRNAs are associated with trimethylated H3K4 histones and histone methyltransferase MLL1, suggesting a role in epigenetic regulation of homeotic loci during ES cell differentiation. Taken together, our data indicate that long ncRNAs are likely to be important in processes directing pluripotency and alternative differentiation programs, in some cases through engagement of the epigenetic machinery.

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MicroRNA Expression Pattern of Undifferentiated and Differentiated Human Embryonic Stem Cells

Cited by 179 publications

References 68 publications

Characterization of microRNAs Involved in Embryonic Stem Cell States

Characterization of microRNAs Involved in Embryonic Stem Cell States

Concise Review: MicroRNA Expression in Multipotent Mesenchymal Stromal Cells

Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation

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