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DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal.

Nature genetics | February 26, 2007 |

Wang, Yangming | Medvid, Rostislav | Melton, Collin | Jaenisch, Rudolf | Blelloch, Robert
Wang, Medvid, et al. "DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal." Nature genetics 39.3 (2007): 380-5. Web.

Abstract

The molecular controls that govern the differentiation of embryonic stem (ES) cells remain poorly understood. DGCR8 is an RNA-binding protein that assi ... ction. Our findings indicate that miRNAs function in the silencing of ES cell self-renewal that normally occurs with the induction of differentiation.

The molecular controls that govern the differentiation of embryonic stem (ES) cells remain poorly understood. DGCR8 is an RNA-binding protein that assists the RNase III enzyme Drosha in the processing of microRNAs (miRNAs), a subclass of small RNAs. Here we study the role of miRNAs in ES cell differentiation by generating a Dgcr8 knockout model. Analysis of mouse knockout ES cells shows that DGCR8 is essential for biogenesis of miRNAs. On the induction of differentiation, DGCR8-deficient ES cells do not fully downregulate pluripotency markers and retain the ability to produce ES cell colonies; however, they do express some markers of differentiation. This phenotype differs from that reported for Dicer1 knockout cells, suggesting that Dicer has miRNA-independent roles in ES cell function. Our findings indicate that miRNAs function in the silencing of ES cell self-renewal that normally occurs with the induction of differentiation.

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Nihms206127f1
Fig 1. Wang, Medvid, et al. "DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal." Nature genetics 39.3 (2007): 380-5. Web.
Nihms206127f1
Fig 1. Wang, Medvid, et al. "DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal." Nature genetics 39.3 (2007): 380-5. Web.

Fig 1

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Fig 2. Wang, Medvid, et al. "DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal." Nature genetics 39.3 (2007): 380-5. Web.
Nihms206127f2
Fig 2. Wang, Medvid, et al. "DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal." Nature genetics 39.3 (2007): 380-5. Web.

Fig 2

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Nihms206127f3
Fig 3. Wang, Medvid, et al. "DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal." Nature genetics 39.3 (2007): 380-5. Web.
Nihms206127f3
Fig 3. Wang, Medvid, et al. "DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal." Nature genetics 39.3 (2007): 380-5. Web.

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Nihms206127f4
Fig 4. Wang, Medvid, et al. "DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal." Nature genetics 39.3 (2007): 380-5. Web.
Nihms206127f4
Fig 4. Wang, Medvid, et al. "DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal." Nature genetics 39.3 (2007): 380-5. Web.

Fig 4

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Nihms206127f5
Fig 5. Wang, Medvid, et al. "DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal." Nature genetics 39.3 (2007): 380-5. Web.
Nihms206127f5
Fig 5. Wang, Medvid, et al. "DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal." Nature genetics 39.3 (2007): 380-5. Web.

Fig 5

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