Human long non-coding RNAs promote pluripotency and neuronal differentiation by association with chromatin modifiers and transcription factors

• Published in: The EMBO journal 2012-02, Vol.31 (3), p.522-533
• Main Authors: Ng, Shi-Yan, Johnson, Rory, Stanton, Lawrence W
• Format: Article
• Language: English
• Subjects: Cell Differentiation - genetics; Chromatin; Chromatin - metabolism; EMBO09; EMBO27; EMBO36; Fluorescent Antibody Technique; Gene Knockdown Techniques; Genomics; Humans; long non-coding RNAs; Molecular biology; neurogenesis; Neurology; Neurons - cytology; Oligonucleotide Array Sequence Analysis; pluripotency; PRC2; Ribonucleic acid; RNA; RNA, Untranslated - genetics; RNA, Untranslated - metabolism; RNA, Untranslated - physiology; SOX2; Stem cells; Transcription Factors - metabolism
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/emboj.2011.459

Long non‐coding RNAs (lncRNAs) are a numerous class of newly discovered genes in the human genome, which have been proposed to be key regulators of biological processes, including stem cell pluripotency and neurogenesis. However, at present very little functional characterization of lncRNAs in human differentiation has been carried out. In the present study, we address this using human embryonic stem cells (hESCs) as a paradigm for pluripotency and neuronal differentiation. With a newly developed method, hESCs were robustly and efficiently differentiated into neurons, and we profiled the expression of thousands of lncRNAs using a custom‐designed microarray. Some hESC‐specific lncRNAs involved in pluripotency maintenance were identified, and shown to physically interact with SOX2, and PRC2 complex component, SUZ12. Using a similar approach, we identified lncRNAs required for neurogenesis. Knockdown studies indicated that loss of any of these lncRNAs blocked neurogenesis, and immunoprecipitation studies revealed physical association with REST and SUZ12. This study indicates that lncRNAs are important regulators of pluripotency and neurogenesis, and represents important evidence for an indispensable role of lncRNAs in human brain development. An array‐based approach identifies hESC‐specific novel long non‐coding RNAs (lncRNAs) that are essential for the maintenance of pluripotency and indispensable for neuronal differentiation. A number of these lncRNAs directly interact with the pluripotency regulators SOX2 and PRC2.