Transcriptomics

Dataset Information

593

Mouse CD4+/CD8+ thymocytes from miR-181a1/b1 KO vs WT


ABSTRACT: miR-181a1/b1, miR-181a2/b2, and miR-181c/d belong to a highly conserved family of microRNA clusters, yet their role in vivo is poorly understood. Here we show that the miR-181a1/b1 cluster is absolutely essential for NKT development and is a critical determinant of thymocyte proliferation, survival and T-cell receptor α locus rearrangement. Furthermore, while individual ablation of miR-181a2/b2 and miR-181c/d revealed no overt phenotypes, compound mutant mice lacking both miR-181a1/b1 and miR-181a2/b2 display decreased survival, reduced body weight, and abnormal B cell development. Mechanistically, we reveal that miR-181 regulates PTEN, a key tumor suppressor whose abundance determines key metabolic adaptations required to meet the biosynthetic demands of highly proliferative tissues. These results provide important insights into the physiological function of this family of microRNAs in vivo; moreover, it places miR-181 as a central regulator of the PI3K signaling pathway and cellular metabolism. Three sorted populations of double positive (DP) thymocytes from each of two conditions (WT and miR181a1/b1 -/- mice)

REANALYSED by: E-GEOD-41090

ORGANISM(S): Mus musculus  

SUBMITTER: John L Rinn   Adam Williams  Jorge Henao-Mejia  Loyal A Goff  Maki Nakayama  Richard A Flavel  Paula Licona-Limon  Matthew Staron  Susan M Kaech 

PROVIDER: E-GEOD-41090 | ArrayExpress | 2014-04-09

SECONDARY ACCESSION(S): SRP015851GSE41090PRJNA175759

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

The microRNA miR-181 is a critical cellular metabolic rheostat essential for NKT cell ontogenesis and lymphocyte development and homeostasis.

Henao-Mejia Jorge J   Williams Adam A   Goff Loyal A LA   Staron Matthew M   Licona-Limón Paula P   Kaech Susan M SM   Nakayama Maki M   Rinn John L JL   Flavell Richard A RA  

Immunity 20130425 5


Regulation of metabolic pathways in the immune system provides a mechanism to actively control cellular function, growth, proliferation, and survival. Here, we report that miR-181 is a nonredundant determinant of cellular metabolism and is essential for supporting the biosynthetic demands of early NKT cell development. As a result, miR-181-deficient mice showed a complete absence of mature NKT cells in the thymus and periphery. Mechanistically, miR-181 modulated expression of the phosphatase PTE  ...[more]

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