MicroRNA/mRNA regulatory networks in the control of skin development and regeneration

Botchkareva, Natalia V.

doi:10.4161/cc.11.3.19058

Cited by 55 publications

(39 citation statements)

References 62 publications

(102 reference statements)

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“…In somatic stem cells, the roles of miRNAs in promoting differentiation have been reported in numerous tissues, including skin (Botchkareva, 2012;Lena et al, 2008;Ning and Andl, 2012;Yi et al, 2008), brain (Cheng et al, 2009;Zhao et al, 2009) and skeletal muscle . However, two important questions about the role of miRNAs in the differentiation of stem cells remain unanswered.…”

Section: Discussionmentioning

confidence: 99%

Rapid and widespread suppression of self-renewal by microRNA-203 during epidermal differentiation

et al. 2013

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SUMMARYMicroRNAs (miRNAs) play important roles in differentiation of stem cells. However, the precise dynamics of miRNA induction during stem cell differentiation have not been visualized and molecular mechanisms through which miRNAs execute their function remain unclear. Using high-resolution in situ hybridization together with cell lineage and proliferation markers in mouse skin, we show that miR-203 is transcriptionally activated in the differentiating daughter cells upon the asymmetric cell division of interfollicular progenitor cells. Once induced, miR-203 rapidly promotes the cell cycle exit within 6 hours and abolishes self-renewal of the progenitor cells. With an inducible mouse model, we identify numerous miR-203 in vivo targets that are highly enriched in regulation of cell cycle and cell division, as well as in response to DNA damage. Importantly, co-suppression of individual targets, including p63, Skp2 and Msi2 by miR-203 is required for its function of promoting the cell cycle exit and inhibiting the long-term proliferation. Together, our findings reveal the rapid and widespread impact of miR-203 on the self-renewal program and provide mechanistic insights into the potent role of miR-203 during the epidermal differentiation. These results should also contribute to understanding the role of miR-203 in the development of skin cancer.

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Section: Discussionmentioning

confidence: 99%

Rapid and widespread suppression of self-renewal by microRNA-203 during epidermal differentiation

et al. 2013

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“…Conditional deletion of genes encoding Dicer and DiGeorge syndrome critical region gene 8 (Dgcr8), key proteins involved in miRNA biogenesis, revealed important roles of miRNAs in mammalian skin development and function 21,22 . Furthermore, miRNAs are regulators of keratinocyte proliferation and differentiation in normal and wounded skin, as well as in autoimmune and chronic skin diseases [23][24][25] . Therefore, we decided to study the role of Nrf2 in the control of miRNA expression in the skin.…”

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confidence: 99%

A novel Nrf2-miR-29-desmocollin-2 axis regulates desmosome function in keratinocytes

et al. 2014

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The Nrf2 transcription factor controls the expression of genes involved in the antioxidant defense system. Here, we identified Nrf2 as a novel regulator of desmosomes in the epidermis through the regulation of microRNAs. On Nrf2 activation, expression of miR-29a and miR-29b increases in cultured human keratinocytes and in mouse epidermis. Chromatin immunoprecipitation identified the Mir29ab1 and Mir29b2c genes as direct Nrf2 targets in keratinocytes. While binding of Nrf2 to the Mir29ab1 gene activates expression of miR-29a and -b, the Mir29b2c gene is silenced by DNA methylation. We identified desmocollin-2 (Dsc2) as a major target of Nrf2-induced miR-29s. This is functionally important, since Nrf2 activation in keratinocytes of transgenic mice causes structural alterations of epidermal desmosomes. Furthermore, the overexpression of miR-29a/b or knockdown of Dsc2 impairs the formation of hyper-adhesive desmosomes in keratinocytes, whereas Dsc2 overexpression has the opposite effect. These results demonstrate that a novel Nrf2-miR-29-Dsc2 axis controls desmosome function and cutaneous homeostasis.

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“…8 The microRNAs also are effective in promoting the differentiation of somatic stem cells to neurons, cardiomyocytes, skin, and brain tissue. [27][28][29][30][31][32] In addition, microRNAsplay a critical role in pancreatic development. 13,[33][34][35][36] However, the actions of microRNAs in the differentiation process are poorly understood.…”

Section: Discussionmentioning

confidence: 99%

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Shaer

Azarpira

Karimi³

et al. 2016

Exp Clin Transplant

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Objectives: Diabetes results from inadequate insulin production from pancreatic ß-cells. Islet cell replacement is an effective approach for diabetes treatment; however, it is not sufficient for all diabetic patients. Thus, finding a new source with effective maturation of ß-cells is the major goal of many studies. MicroRNAs are a class of small noncoding ribonucleic acid that regulate gene expression through posttranscriptional mechanisms. MicroRNA-7 has high expression level during pancreatic islet development in humans, thereby playing a critical role in pancreatic β-cell function. We study aimed to develop a protocol to differentiate human-induced pluripotent stem cells efficiently into isletlike cell clusters in vitro by using microRNA-7. Materials and Methods: Human-induced pluripotent stem cell colonies were transfected with hsamicroRNA-7 by using siPORT NeoFX transfection agent. Total ribonucleic acid was extracted 24 and 48 hours after transfection. The expression of transcription factors which were important during pancreases development was also performed. On the third day, the potency of the clusters was assessed in response to high glucose levels. Diphenylthiocarbazone was used to identify the existence of the ß-cells. The presence of insulin and Neurogenin-3 proteins was investigated by immunocytochemistry. Results: Morphologic changes were observed on the first day after chemical transfection, and cell clusters were formed on the third day. The expression of pancreatic specific transcription factors was increased on the first day and significantly increased on the second day. The isletlike cell clusters were positive for insulin and Neurogenin-3 proteins in immunocytochemistry. The clusters were stained with Diphenylthiocarbazone and secreted insulin in a glucose challenge test. Conclusions: MicroRNA-7 transcription factor net-work is important in pancreatic endocrine differe-ntiation. Chemical transfection with microRNA-7 can differentiate human induced pluripotent stem cells into functional isletlike cell clusters in a short time.

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MicroRNA/mRNA regulatory networks in the control of skin development and regeneration

Cited by 55 publications

References 62 publications

Rapid and widespread suppression of self-renewal by microRNA-203 during epidermal differentiation

Rapid and widespread suppression of self-renewal by microRNA-203 during epidermal differentiation

A novel Nrf2-miR-29-desmocollin-2 axis regulates desmosome function in keratinocytes

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