Co-existence of Intact Stemness and Priming of Neural Differentiation Programs in MES Cells Lacking Trim71

Overview

Journal Sci Rep

Specialty Science

Date 2015 Jun 10

PMID 26057209

Citations 26

Authors

Sibylle Mitschka

Thomas Ulas

Tobias Goller

Karin Schneider

Angela Egert

Jerome Mertens

Oliver Brustle

Hubert Schorle

Marc Beyer

Kathrin Klee

Jia Xue

Patrick Gunther

Kevin Bassler

Joachim L Schultze

Waldemar Kolanus

Affiliations

Soon will be listed here.

Abstract

Regulatory networks for differentiation and pluripotency in embryonic stem (ES) cells have long been suggested to be mutually exclusive. However, with the identification of many new components of these networks ranging from epigenetic, transcriptional, and translational to even post-translational mechanisms, the cellular states of pluripotency and early differentiation might not be strictly bi-modal, but differentiating stem cells appear to go through phases of simultaneous expression of stemness and differentiation genes. Translational regulators such as RNA binding proteins (RBPs) and micro RNAs (miRNAs) might be prime candidates for guiding a cell from pluripotency to differentiation. Using Trim71, one of two members of the Tripartite motif (Trim) protein family with RNA binding activity expressed in murine ES cells, we demonstrate that Trim71 is not involved in regulatory networks of pluripotency but regulates neural differentiation. Loss of Trim71 in mES cells leaves stemness and self-maintenance of these cells intact, but many genes required for neural development are up-regulated at the same time. Concordantly, Trim71(-/-) mES show increased neural marker expression following treatment with retinoic acid. Our findings strongly suggest that Trim71 keeps priming steps of differentiation in check, which do not pre-require a loss of the pluripotency network in ES cells.

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