Role of MicroRNAs 99b, 181a, and 181b in the Differentiation of Human Embryonic Stem Cells to Vascular Endothelial Cells

Kane, Nicole M.; Howard, Lynsey; Descamps, B; Meloni, Marco; McClure, John; Lu, Ruifang; McCahill, Angela; Breen, Christopher R; Mackenzie, Ruth M.; Delles, Christian; Mountford, Joanne C.; Milligan, Graeme; Emanueli, Costanza; Baker, Andrew H.

doi:10.1002/stem.1026

Cited by 91 publications

(85 citation statements)

References 59 publications

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“…4a-c). To test the loss-of-function effect of miR-574-5p in neurogenesis, we transfect NPCs with an anti-miR-574-5p-expressing vector (miR-Zip), which is designed to bind directly to miR-574-5p and inhibits its function 12 . The knockdown efficiency of miR-574-5p after transfection with miRZip-574-5p is confirmed by qPCR to be B60% ( Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Amyloid precursor protein regulates neurogenesis by antagonizing miR-574-5p in the developing cerebral cortex

et al. 2014

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Amyloid precursor protein (APP) is a transmembrane glycoprotein proteolytically processed to release amyloid beta, a pathological hallmark of Alzheimer's disease. APP is expressed throughout the developing and mature brain; however, the primary function of this protein is unknown. We previously demonstrated that APP deficiency enhances neurogenesis, but the mechanisms underlying this process are not known. Here we show that APP regulates the expression of microRNAs in the cortex and in neural progenitors, specifically repressing miR-574-5p. We also show that overexpression of miR-574-5p promotes neurogenesis, but reduces the neural progenitor pool. In contrast, the reduced expression of miR-574-5p inhibits neurogenesis and stimulates proliferation in vitro and in utero. We further demonstrate that the inhibition of miR-574-5p in APP-knockout mice rescues the phenotypes associated with APP deficiency in neurogenesis. Taken together, these results reveal a mechanism in which APP regulates the neurogenesis through miRNA-mediated post-transcriptional regulation.

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Section: Resultsmentioning

confidence: 99%

Amyloid precursor protein regulates neurogenesis by antagonizing miR-574-5p in the developing cerebral cortex

et al. 2014

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“…In human ESCs, miR-99b, miR-181a and miR-181b regulated the mRNA and protein expression of EC-specific markers, increased nitric oxide production, and improved therapeutic neovascularization in vivo [62] . In addition, the expression of miR-7641 was downregulated during the endothelial differentiation of human ESCs.…”

Section: Endothelial Cell Differentiationmentioning

confidence: 97%

MicroRNAs as novel regulators of stem cell fate

Choi

Hwang³

2013

WJSC

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Mounting evidence in stem cell biology has shown that microRNAs (miRNAs) play a crucial role in cell fate specification, including stem cell self-renewal, lineagespecific differentiation, and somatic cell reprogramming. These functions are tightly regulated by specific gene expression patterns that involve miRNAs and transcription factors. To maintain stem cell pluripotency, specific miRNAs suppress transcription factors that promote differentiation, whereas to initiate differentiation, lineagespecific miRNAs are upregulated via the inhibition of transcription factors that promote self-renewal. Small molecules can be used in a similar manner as natural miRNAs, and a number of natural and synthetic small molecules have been isolated and developed to regulate stem cell fate. Using miRNAs as novel regulators of stem cell fate will provide insight into stem cell biology and aid in understanding the molecular mechanisms and crosstalk between miRNAs and stem cells.Ultimately, advances in the regulation of stem cell fate will contribute to the development of effective medical therapies for tissue repair and regeneration. This review summarizes the current insights into stem cell fate determination by miRNAs with a focus on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted.© 2013 Baishideng. All rights reserved. Key words:MicroRNA; Stem cell fate; Differentiation; Self-renewal; Reprogramming; Small molecule Core tip: Stem cells are important in regenerative medicine applications due to their capacity to self-renew and differentiate into specific cell types. MicroRNAs (miRNAs) are short non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. Recent studies suggest that miRNAs are key molecules in the regulation of stem cell fate decisions; this regulation is manifested as the fine tuning of cell-and tissue-specific gene expression. This review summarizes the current insights into stem cell fate determination by miRNAs and focuses on stem cell self-renewal, differentiation, and reprogramming. Small molecules that control stem cell fate are also highlighted.

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“…Overexpression of these miRs potentiated generation of ESC-ECs and improved their angiogenic capacity in a murine model of hindlimb ischemia. 44 More recently, miR-21 has also been highlighted as mediating EC generation from iPSCs, through upregulation of transforming growth factor (TGF)-β2 pathway signaling. 45 Just as specialized ECs in prenatal development give rise to hematopoietic and possibly mesenchymal progeny (Online Data Supplement), there is also the intriguing postnatal phenomenon of endothelial-to-mesenchymal transformation, whereby ECs detach from neighboring cells before undergoing morphological and cytoskeletal transformation to mesenchymal phenotypes.…”

Section: Cd45mentioning

confidence: 99%

Vascular Wall Progenitor Cells in Health and Disease

Psaltis

Simari

2015

Circulation Research

172

155

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The vasculature plays an indispensible role in organ development and maintenance of tissue homeostasis, such that disturbances to it impact greatly on developmental and postnatal health. Although cell turnover in healthy blood vessels is low, it increases considerably under pathological conditions. The principle sources for this phenomenon have long been considered to be the recruitment of cells from the peripheral circulation and the re-entry of mature cells in the vessel wall back into cell cycle. However, recent discoveries have also uncovered the presence of a range of multipotent and lineage-restricted progenitor cells in the mural layers of postnatal blood vessels, possessing high proliferative capacity and potential to generate endothelial, smooth muscle, hematopoietic or mesenchymal cell progeny. In particular, the tunica adventitia has emerged as a progenitor-rich compartment with niche-like characteristics that support and regulate vascular wall progenitor cells. Preliminary data indicate the involvement of some of these vascular wall progenitor cells in vascular disease states, adding weight to the notion that the adventitia is integral to vascular wall pathogenesis, and raising potential implications for clinical therapies. This review discusses the current body of evidence for the existence of vascular wall progenitor cell subpopulations from development to adulthood and addresses the gains made and significant challenges that lie ahead in trying to accurately delineate their identities, origins, regulatory pathways, and relevance to normal vascular structure and function, as well as disease.

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Role of MicroRNAs 99b, 181a, and 181b in the Differentiation of Human Embryonic Stem Cells to Vascular Endothelial Cells

Cited by 91 publications

References 59 publications

Amyloid precursor protein regulates neurogenesis by antagonizing miR-574-5p in the developing cerebral cortex

Amyloid precursor protein regulates neurogenesis by antagonizing miR-574-5p in the developing cerebral cortex

MicroRNAs as novel regulators of stem cell fate

Vascular Wall Progenitor Cells in Health and Disease

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