Dataset Information

MicroRNA-dependent regulation of biomechanical genes establishes tissue stiffness homeostasis

ABSTRACT: microRNA-dependent regulation of biomechanical genes establishes tissue stiffness homeostasis

OTHER RELATED OMICS DATASETS IN: GSE99686

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Huvec Cell

SUBMITTER: Craig Lawless

LAB HEAD: Stefanie Nicoli

PROVIDER: PXD011882 | Pride | 2019-02-19

REPOSITORIES: Pride

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MicroRNA-dependent regulation of biomechanical genes establishes tissue stiffness homeostasis.

Moro Albertomaria A Driscoll Tristan P TP Boraas Liana C LC Armero William W Kasper Dionna M DM Baeyens Nicolas N Jouy Charlene C Mallikarjun Venkatesh V Swift Joe J Ahn Sang Joon SJ Lee Donghoon D Zhang Jing J Gu Mengting M Gerstein Mark M Schwartz Martin M Nicoli Stefania S

Nature cell biology 20190211 3

Vertebrate tissues exhibit mechanical homeostasis, showing stable stiffness and tension over time and recovery after changes in mechanical stress. However, the regulatory pathways that mediate these effects are unknown. A comprehensive identification of Argonaute 2-associated microRNAs and mRNAs in endothelial cells identified a network of 122 microRNA families that target 73 mRNAs encoding cytoskeletal, contractile, adhesive and extracellular matrix (CAM) proteins. The level of these microRNAs ...[more]

PMID: 30742093

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Project description:Since the first generation of induced Pluripotent Stem cells (iPSCs), several reprogramming systems have been used to study its molecular mechanisms. However, the system of choice largely affects the reprogramming efficiency, influencing our view on the mechanisms. Here we demonstrate that reprogramming triggered by less efficient polycistronic reprogramming cassettes not only highlights Mesenchymal-Epithelial Transition (MET) as a roadblock, but also faces more severe difficulties to attain a pluripotent state even post-MET. Also, in contrast to previous findings, more efficient cassettes can reprogram both wild type and Nanog-/- fibroblasts with comparable efficiencies, routes and kinetics, rebutting previous studies that Nanog is critical for iPSC generation. We revealed that the 9 amino acids in the N-terminus of Klf4 in polycistronic reprogramming cassettes are the dominant factor causing these critical differences. Our data establishes that some reprogramming roadblocks are system-dependent, highlighting the need to pursue mechanistic studies with close attention to the systems to better understand reprogramming. The aim of the experiment is to compare the reprogramming pathways driven by two different polycistronic cassettes (MKOS and OKMS). We have isolated cells at intermediate stages of both MKOS and OKMS reprogramming and analysed their gene expression profiles. 2N- are CD44- ICAM1-, Nanog-GFP-, 3N- are CD44- ICAM1+, Nanog-GFP-, 3N+ are CD44- ICAM1+, Nanog-GFP+, all from day 10 of reprogramming. MKOS/OKMS iPSCs are established iPSC clones, TNG an Embryonic Stem Cell line carrying a Nanog-GFP reporter published in Chambers et al. Cell, 113, 643-655, from this line TNG MKOS and OKMS Embryonic Stem Cells were generated after targeting the Sp3 locus with the MKOS or the OKMS cassette respectively,E14 a reference Embryonic Stem Cell line and MEF are Mouse Embryonic Fibroblasts either wild type or generaterd from TNG MKOS or OKMS ESCs. D6 is the D6s4B5 iPSC line published in O'Malley et al. Nature, 499, 88-91.

Dataset Information

MicroRNA-dependent regulation of biomechanical genes establishes tissue stiffness homeostasis

Publications

MicroRNA-dependent regulation of biomechanical genes establishes tissue stiffness homeostasis.

Similar Datasets

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