MicroRNA Profiling of Human-Induced Pluripotent Stem Cells

Wilson, Kitchener D.; Venkatasubrahmanyam, Shivkumar; Jia, Fangjun; Sun, Ninghui; Butte, Atul J.; Wu, Joseph C.

doi:10.1089/scd.2008.0247

Cited by 218 publications

(201 citation statements)

References 42 publications

Supporting

Mentioning

184

Contrasting

Unclassified

Order By: Relevance

“…A recent report indicated that some hESC-enriched miRNAs, including the miR-371-373 cluster, are differentially expressed in iPSCs as compared with hESCs [ 55 ]. We tested whether butyrate treatment can similarly up-regulate expression of the miR-371-373 cluster in iPSC lines.…”

Section: Figmentioning

confidence: 98%

Characterization of microRNAs Involved in Embryonic Stem Cell States

Stadler

Ivanovska²,

Mehta

et al. 2010

Stem Cells and Development

153

165

View full text Add to dashboard Cite

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.

show abstract

Section: Figmentioning

confidence: 98%

Characterization of microRNAs Involved in Embryonic Stem Cell States

Stadler

Ivanovska²,

Mehta

et al. 2010

Stem Cells and Development

153

165

View full text Add to dashboard Cite

show abstract

“…Importantly, besides protein-coding genes, miRNA expression profiles also differ between current iPS and ES cell clones [61,67]. It should be noted though, that recent experiments profiling miRNA levels in large number of pluripotent cell lines (both human iPS and ES cells) suggest that differentially expressed miRNAs subdivide the pluripotent cells into two groups, irrespective of their induced pluripotent-or embryoderived origin, but reflecting their p53 network status [68].…”

Section: Are We There Yet? Are Es and Ips Cells Equivalent?mentioning

confidence: 99%

Reprogramming to pluripotency: stepwise resetting of the epigenetic landscape

2011

View full text Add to dashboard Cite

In 2006, the "wall came down" that limited the experimental conversion of differentiated cells into the pluripotent state. In a landmark report, Shinya Yamanaka's group described that a handful of transcription factors (Oct4, Sox2, Klf4 and c-Myc) can convert a differentiated cell back to pluripotency over the course of a few weeks, thus reprograming them into induced pluripotent stem (iPS) cells. The birth of iPS cells started off a rush among researchers to increase the efficiency of the reprogramming process, to reveal the underlying mechanistic events, and allowed the generation of patient-and disease-specific human iPS cells, which have the potential to be converted into relevant specialized cell types for replacement therapies and disease modeling. This review addresses the steps involved in resetting the epigenetic landscape during reprogramming. Apparently, defined events occur during the course of the reprogramming process. Immediately, upon expression of the reprogramming factors, some cells start to divide faster and quickly begin to lose their differentiated cell characteristics with robust downregulation of somatic genes. Only a subset of cells continue to upregulate the embryonic expression program, and finally, pluripotency genes are upregulated establishing an embryonic stem cell-like transcriptome and epigenome with pluripotent capabilities. Understanding reprogramming to pluripotency will inform mechanistic studies of lineage switching, in which differentiated cells from one lineage can be directly reprogrammed into another without going through a pluripotent intermediate.

show abstract

“…Since miRNAs can function by maintaining terminal differentiation and inducing developmental transitions, there has been a growing interest in miRNAs for stimulating stem cells to adopt specific lineages, reprogramming of differentiated cells to induce pluripotency [18][19][20] and, in general, for improving our understanding of stem cell biology [21][22][23]. As drivers or mediators of pathology, miRNAs are promising therapeutic targets.…”

mentioning

confidence: 99%

Epigenetics and ncRNAs in Brain Function and Disease: Mechanisms and Prospects for Therapy

2013

View full text Add to dashboard Cite

The most fundamental roles of non-coding RNAs (ncRNAs) and epigenetic mechanisms are the guidance of cellular differentiation in development and the regulation of gene expression in adult tissues. In brain, both ncRNAs and the various epigenetic gene regulatory mechanisms play a fundamental role in neurogenesis and normal neuronal function. Thus, epigenetic chromatin remodelling can render coding sites transcriptionally inactive by DNA methylation, histone modifications or antisense RNA interactions. On the other hand, microRNAs (miRNAs) are ncRNA molecules that can regulate the expression of hundreds of genes post-transcriptionally, typically recognising binding sites in the 3′ untranslated region (UTR) of mRNA transcripts. Furthermore, there are a myriad of interactions in the interface of miRNAs and epigenetics. For example, epigenetic mechanisms can silence miRNA coding sites, and miRNAs can be the effectors of transcriptional gene silencing, targeting complementary promoters or silencing the expression of epigenetic modifier genes like MECP2 and EZH2 leading to global changes in the epigenome. Alterations in this regulatory machinery play a key role in the pathology of complex disorders including cancer and neurological diseases. For example, miRNA genes are frequently inactivated by epimutations in gliomas. Here we describe the interactions between epigenetic and ncRNA regulatory systems and discuss therapeutic potential, with an emphasis on tumors, cognitive disorders and neurodegenerative diseases.

show abstract

MicroRNA Profiling of Human-Induced Pluripotent Stem Cells

Cited by 218 publications

References 42 publications

Characterization of microRNAs Involved in Embryonic Stem Cell States

Characterization of microRNAs Involved in Embryonic Stem Cell States

Reprogramming to pluripotency: stepwise resetting of the epigenetic landscape

Epigenetics and ncRNAs in Brain Function and Disease: Mechanisms and Prospects for Therapy

Contact Info

Product

Resources

About