Human long non‐coding RNAs promote pluripotency and neuronal differentiation by association with chromatin modifiers and transcription factors
Open accessAbstract
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.
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RNAi knockdown of some lncRNAs impairs neuronal differentiation, suggesting that lncRNAs play critical roles in neurogenesis.
“RNAi knockdown of some lncRNAs impairs neuronal differentiation, suggesting that lncRNAs play critical roles in neurogenesis.305”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [305]
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Cites
Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis
Gupta, R. A., Shah, N., Wang, K., Kim, J., Horlings, H. M., Wong, D. J., Tsai, M.-C., Hung, T., Argani, P., Rinn, J. L., et al. (2010) · Nature · doi:10.1038/nature08975 · Cited by 5,203 · see citing works
Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals
Guttman, M., Amit, I., Garber, M., French, C., Lin, M. F., Feldser, D., Huarte, M., Zuk, O., Carey, B. W., Cassady, J. P., et al. (2009) · Nature · doi:10.1038/nature07672 · Cited by 4,098 · see citing works
The Transcriptional Landscape of the Mammalian Genome
Carninci, P., Kasukawa, T., Katayama, S., Gough, J., Frith, M. C., Maeda, N., Oyama, R., Ravasi, T., Lenhard, B., Wells, C. A., et al. (2005) · Science · doi:10.1126/science.1112014 · Cited by 3,492 · see citing works
Long Noncoding RNA as Modular Scaffold of Histone Modification Complexes
Tsai, M.-C., Manor, O., Wan, Y., Mosammaparast, N., Wang, J. K., Lan, F., Shi, Y., Segal, E., & Chang, H. Y. (2010) · Science · doi:10.1126/science.1192002 · Cited by 3,290 · cited 5× · see citing works
“…biological processes that coordinate gene expression, through epigenetic modification (Khalil et al , 2009; Gupta et al , 2010; Mohammad et al , 2010; Tsai et al , 2010; Wang et al , 2011), mRNA splicing (Tripathi et al , 2010), control of transcription (Orom et al , 2010) or translation (Gong…”
InfluentialKhalil, A. M., Guttman, M., Huarte, M., Garber, M., Raj, A., Rivea Morales, D., Thomas, K., Presser, A., Bernstein, B. E., van Oudenaarden, A., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904715106 · Cited by 2,872 · see citing works
Kong, L., Zhang, Y., Ye, Z., Liu, X., Zhao, S.-Q., Wei, L., & Gao, G. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm391 · Cited by 2,773 · see citing works
Long noncoding RNAs: functional surprises from the RNA worldPreprint
Wilusz, J. E., Sunwoo, H., & Spector, D. L. (2009) · Genes & Development · doi:10.1101/gad.1800909 · Cited by 2,298 · see citing works
Tripathi, V., Ellis, J. D., Shen, Z., Song, D. Y., Pan, Q., Watt, A. T., Freier, S. M., Bennett, C. F., Sharma, A., Bubulya, P. A., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.08.011 · Cited by 2,223 · see citing works
A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression
Wang, K., Yang, Y. W., Liu, B., Sanyal, A., Corces, M. R., Chen, Y., Lajoie, B. R., Protacio, A., Flynn, R. A., Gupta, R. A., et al. (2011) · Nature · doi:10.1038/nature09819 · Cited by 1,963 · see citing works
lincRNAs act in the circuitry controlling pluripotency and differentiation
Guttman, M., Donaghey, J., Carey, B. W., Garber, M. G., Grenier, J. K., Munson, G., Young, G., Lucas, A. B., Ach, R. A., Bruhn, L., et al. (2011) · Nature · doi:10.1038/nature10398 · Cited by 1,845 · see citing works
Long Noncoding RNAs with Enhancer-like Function in Human Cells
Ørom, U. A., Derrien, T., Beringer, M., Gumireddy, K., Gardini, A., Bussotti, G., Lai, F., Zytnicki, M., Notredame, C., Huang, Q., et al. (2010) · Cell · doi:10.1016/j.cell.2010.09.001 · Cited by 1,721 · see citing works
Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture
Ying, Q.-L., Stavridis, M., Griffiths, D., Li, M., & Smith, A. (2003) · Nature Biotechnology · doi:10.1038/nbt780 · Cited by 1,504 · see citing works
Induction of Midbrain Dopaminergic Neurons from ES Cells by Stromal Cell–Derived Inducing Activity
Kawasaki, H., Mizuseki, K., Nishikawa, S., Kaneko, S., Kuwana, Y., Nakanishi, S., Nishikawa, S., & Sasai, Y. (2000) · Neuron · doi:10.1016/s0896-6273(00)00083-0 · Cited by 1,277 · see citing works
lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3′ UTRs via Alu elements
Gong, C., & Maquat, L. E. (2011) · Nature · doi:10.1038/nature09701 · Cited by 1,261 · see citing works
Pandey, R. R., Mondal, T., Mohammad, F., Enroth, S., Redrup, L., Komorowski, J., Nagano, T., Mancini‐DiNardo, D., & Kanduri, C. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.08.022 · Cited by 1,192 · see citing works
Specific expression of long noncoding RNAs in the mouse brain
Mercer, T. R., Dinger, M. E., Sunkin, S. M., Mehler, M. F., & Mattick, J. S. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706729105 · Cited by 1,103 · see citing works
Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells
Loewer, S., Cabili, M. N., Guttman, M., Loh, Y., Thomas, K., Park, I. H., Garber, M. G., Curran, M. S., Önder, T. T., Agarwal, S., et al. (2010) · Nature Genetics · doi:10.1038/ng.710 · Cited by 971 · see citing works
Rybak‐Wolf, A., Fuchs, H. R., Smirnova, L., Brandt, C., Pohl, E. E., Nitsch, R., & Wulczyn, F. G. (2008) · Nature Cell Biology · doi:10.1038/ncb1759 · Cited by 788 · see citing works
A long nuclear‐retained non‐coding RNA regulates synaptogenesis by modulating gene expression
Bernard, D., Prasanth, K. V., Tripathi, V., Colasse, S., Nakamura, T., Xuan, Z., Zhang, M. Q., Sedel, F., Jourdren, L., Coulpier, F., et al. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.199 · Cited by 738 · see citing works
Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiationPreprint
Dinger, M. E., Amaral, P., Mercer, T. R., Pang, K. C., Bruce, S. J., Gardiner, B., Askarian-Amiri, M., Ru, K., Soldà, G., Simons, C., et al. (2008) · Genome Research · doi:10.1101/gr.078378.108 · Cited by 729 · see citing works
Rapid evolution of noncoding RNAs: lack of conservation does not mean lack of function
Pang, K. C., Frith, M. C., & Mattick, J. S. (2005) · Trends in Genetics · doi:10.1016/j.tig.2005.10.003 · Cited by 653 · see citing works
Amaral, P., & Mattick, J. S. (2008) · Mammalian Genome · doi:10.1007/s00335-008-9136-7 · Cited by 479 · see citing works
A genome-wide RNAi screen reveals determinants of human embryonic stem cell identity
Chia, N., Chan, Y.-S., Feng, B., Lu, X., Orlov, Y. L., Moreau, D., Kumar, P., Yang, L., Jiang, J., Lau, M.-S., et al. (2010) · Nature · doi:10.1038/nature09531 · Cited by 461 · see citing works
Reversible cross-linking combined with immunoprecipitation to study RNA–protein interactions in vivo
Niranjanakumari, S. (2002) · Methods · doi:10.1016/s1046-2023(02)00021-x · Cited by 410 · see citing works
Bond, A. M., VanGompel, M. J. W., Sametsky, E. A., Clark, M. F., Savage, J. C., Disterhoft, J. F., & Kohtz, J. D. (2009) · Nature Neuroscience · doi:10.1038/nn.2371 · Cited by 399 · see citing works
Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation
Mercer, T. R., Qureshi, I., Gökhan, Ş., Dinger, M. E., Li, G., Mattick, J. S., & Mehler, M. F. (2010) · BMC Neuroscience · doi:10.1186/1471-2202-11-14 · Cited by 394 · see citing works
Genome-wide computational identification and manual annotation of human long noncoding RNA genes
Jia, H., Osak, M., Bogu, G. K., Stanton, L. W., Johnson, R., & Lipovich, L. (2010) · RNA · doi:10.1261/rna.1951310 · Cited by 380 · see citing works
Self-citationPredicting protein associations with long noncoding RNAs
Bellucci, M., Agostini, F., Masin, M., & Tartaglia, G. G. (2011) · Nature Methods · doi:10.1038/nmeth.1611 · Cited by 371 · see citing works
Dopaminergic Differentiation of Human Embryonic Stem Cells
Zeng, X., Cai, J., Chen, J., Luo, Y., You, Z., Fotter, E., Wang, Y., Harvey, B. K., Miura, T., Bäckman, C. M., et al. (2004) · Stem Cells · doi:10.1634/stemcells.22-6-925 · Cited by 370 · see citing works
Ponjavic, J., Oliver, P. L., Lunter, G. A., & Ponting, C. P. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000617 · Cited by 368 · see citing works
Mohamed, J. S., Gaughwin, P. M., Lim, B., Robson, P., & Lipovich, L. (2009) · RNA · doi:10.1261/rna.1441510 · Cited by 335 · see citing works
Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients
Agarwal, S., Loh, Y., McLoughlin, E. M., Huang, J.-J., Park, I.-H., Miller, J. D., Huo, H.-G., Okuka, M., dos Reis, R., Loewer, S., et al. (2010) · Nature · doi:10.1038/nature08792 · Cited by 335 · see citing works
Integrative Annotation of 21,037 Human Genes Validated by Full-Length cDNA Clones
Imanishi, T., Itoh, T., Suzuki, Y., O’Donovan, C., Fukuchi, S., Koyanagi, K. O., Barrero, R. A., Tamura, T., Yamaguchi‐Kabata, Y., Tanino, M., et al. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020162 · Cited by 331 · see citing works
Donato, R., Miljan, E., Hines, S. J., Aouabdi, S., Pollock, K., Patel, S., Edwards, F. A., & Sinden, J. D. (2007) · BMC Neuroscience · doi:10.1186/1471-2202-8-36 · Cited by 308 · see citing works
MicroRNA-125b Promotes Neuronal Differentiation in Human Cells by Repressing Multiple Targets
Le, M. T. N., Xie, H., Zhou, B., Chia, P. H., Rizk, P., Um, M., Udolph, G., Yang, H. H., Lim, B., & Lodish, H. F. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01694-08 · Cited by 288 · see citing works
Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1
Mohammad, F., Mondal, T., Guseva, N., Pandey, G. K., & Kanduri, C. (2010) · Development · doi:10.1242/dev.048181 · Cited by 281 · see citing works
Cho, M. S., Lee, Y. E., Kim, J. Y., Chung, S., Cho, Y. H., Kim, D., Kang, S.-M., Lee, H., Kim, M., Kim, J., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712359105 · Cited by 258 · see citing works
Predicting protein associations with long noncoding RNAs
Bellucci, M., Agostini, F., Masin, M., & Tartaglia, G. G. (2011) · F1000Research · doi:10.7490/f1000research.2007.1 · Cited by 239 · see citing works
Naruse, Y., Aoki, T., Kojima, T., & Mori, N. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.24.13691 · Cited by 229 · see citing works
Redrup, L., Branco, M. R., Perdeaux, E. R., Krueger, C., Lewis, A., Santos, F., Nagano, T., Cobb, B. S., Fraser, P., & Reik, W. (2009) · Development · doi:10.1242/dev.031328 · Cited by 202 · see citing works
The long noncoding RNA RNCR2 directs mouse retinal cell specification
Rapicavoli, N. A., Poth, E. M., & Blackshaw, S. (2010) · BMC Developmental Biology · doi:10.1186/1471-213x-10-49 · Cited by 185 · see citing works
RNA editing, DNA recoding and the evolution of human cognition
Mattick, J. S., & Mehler, M. F. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.02.003 · Cited by 149 · see citing works
Regulation of neural macroRNAs by the transcriptional repressor REST
Johnson, R., Teh, C. H.-L., Jia, H., Vanisri, R. R., Pandey, T., Lu, Z.-H., Buckley, N. J., Stanton, L. W., & Lipovich, L. (2008) · RNA · doi:10.1261/rna.1127009 · Cited by 107 · see citing works
Self-citationSu, X., Kameoka, S., Lentz, S., & Majumder, S. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.18.8018-8025.2004 · Cited by 97 · see citing works
Nkx2.2 antisense RNA overexpression enhanced oligodendrocytic differentiation
Tochitani, S., & Hayashizaki, Y. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.05.127 · Cited by 86 · see citing works
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Kristensen, L. S., Andersen, M. S., Stagsted, L. V. W., Ebbesen, K. K., Hansen, T. B., & Kjems, J. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0158-7 · Cited by 4,823 · see citing works
Long non-coding RNAs: new players in cell differentiation and development
Fatica, A., & Bozzoni, I. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3606 · Cited by 2,980 · see citing works
Long noncoding RNAs: past, present, and future
Kung, J. T. Y., Colognori, D., & Lee, J. T. (2013) · Genetics · doi:10.1534/genetics.112.146704 · Cited by 1,874 · see citing works
Kapusta, A., Kronenberg, Z., Lynch, V. J., Zhuo, X., Ramsay, L., Bourque, G., Yandell, M., & Feschotte, C. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003470 · Cited by 687 · see citing works
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Yu, C.-Y., Li, T.-C., Wu, Y.-Y., Yeh, C.-H., Chiang, W., Chuang, C.-Y., & Kuo, H.-C. (2017) · Nature Communications · doi:10.1038/s41467-017-01216-w · Cited by 336 · see citing works
Yuan, M., Yang, B., Rothschild, G., Mann, J. J., Sanford, L. D., Tang, X., Huang, C., Wang, C., & Zhang, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01519-z · Cited by 246 · see citing works
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Lopez-Pajares, V., Qu, K., Zhang, J., Webster, D. E., Barajas, B. C., Siprashvili, Z., Zarnegar, B. J., Boxer, L. D., Rios, E. J., Tao, S., et al. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.01.028 · Cited by 194 · see citing works
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- Authors
- Ng, S., Johnson, R., & Stanton, L. W.
- Affiliations
- National University of Singapore (SG)
- Universitat Pompeu Fabra (ES)
- Corresponding author
- Stanton, Lawrence W
- Venue
- The EMBO Journal
- Published
- 2011-12-23
- Volume
- 31
- Issue
- 3
- Pages
- 522-533
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC3273385
- OpenAlex
- W2116881442
- Cited by
- 514
- References
- 45
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 15 · 2023: 31 · 2022: 20 · 2021: 41 · 2020: 39 · 2019: 46 · 2018: 35 · 2017: 49 · 2016: 48 · 2015: 47 · 2014: 52 · 2013: 47 · 2012: 23
- FWCI
- 13.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wayne State University
- Agency for Science, Technology and Research
- Biomedical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- long non-coding RNA, human embryonic stem cells, pluripotency, neuronal differentiation, neurogenesis, SOX2, SUZ12, polycomb repressive complex 2, rest, chromatin modifiers, brain development
- MeSH terms
- Cell Differentiation, Chromatin, Fluorescent Antibody Technique, Humans, Neurons, Transcription Factors, Oligonucleotide Array Sequence Analysis, RNA, Untranslated, Gene Knockdown Techniques
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