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MicroRNA profiling of glial progenitor cells in growth and differentiation conditions


ABSTRACT: The molecular basis of astrocyte differentiation and maturation is poorly understood. As microRNAs have important roles in cell fate transitions, we set out to study their function during the glial progenitor cell (GPC) to astrocyte transition. Inducible deletion of all canonical microRNAs in GPCs in vitro led to a block in the differentiation to astrocytes. In an unbiased screen, the reintroduction of let-7 and miR-125 families of microRNAs rescued differentiation. Let-7 and miR-125 shared many targets and functioned in parallel to JAK-STAT signaling, a known regulator of astrogliogenesis. While individual knockdown of shared targets did not rescue the differentiation phenotype in microRNA-deficient GPCs, overexpression of these targets in wild-type GPCs blocked differentiation. This finding supports the idea that microRNAs simultaneously suppress multiple mRNAs that inhibit differentiation. The microRNA-regulated targets were enriched for genes downregulated during in vivo astrocyte differentiation and upregulated in glioblastomas, consistent with validity of using the in vitro model to study in vivo events. These findings provide insight into the microRNAs and the genes they regulate in this important cell fate transition. Small RNA profiling of 2 replicates of GPCs and astrocytes

ORGANISM(S): Mus musculus

SUBMITTER: Robert Blelloch 

PROVIDER: E-GEOD-64661 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Let-7 and miR-125 cooperate to prime progenitors for astrogliogenesis.

Shenoy Archana A   Danial Muhammad M   Blelloch Robert H RH  

The EMBO journal 20150223 9


The molecular basis of astrocyte differentiation and maturation is poorly understood. As microRNAs have important roles in cell fate transitions, we set out to study their function during the glial progenitor cell (GPC) to astrocyte transition. Inducible deletion of all canonical microRNAs in GPCs in vitro led to a block in the differentiation to astrocytes. In an unbiased screen, the reintroduction of let-7 and miR-125 families of microRNAs rescued differentiation. Let-7 and miR-125 shared many  ...[more]

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