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SMN is required for the maintenance of embryonic stem cells and neuronal differentiation in mice

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Abstract

Survival motor neuron (SMN) is the determining factor in spinal muscular atrophy, the most common genetic cause of childhood mortality. We have previously found that SMN regulates stem cell division, proliferation and differentiation in Drosophila. However, it is unknown whether a similar effect exists in vertebrates. Here, we show that SMN is enriched in highly proliferative embryonic stem cells (ESCs) in mice and reduction of SMN impairs the pluripotency of ESCs. Moreover, we find that SMN reduction activates ERK signaling and affects neuronal differentiation in vitro. Teratomas with reduced SMN grow more slowly and show weaker signals of neuronal differentiation than those with a normal level of SMN. Finally, we show that over-expression of SMN is protective for ESCs from retinoic acid-induced differentiation. Taken together, our results suggest that SMN plays a role in the maintenance of pluripotent ESCs and neuronal differentiation in mice.

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Acknowledgments

We thank Kun-Hsiung Lee for providing the trophectoderm stem cells. We also thank Joint Center for Instruments and Researches, College of Bioresources and Agriculture in National Taiwan University for sharing the laser-scanning confocal microscopy facility and providing analysis for flow cytometry. The shRNAs were generated and obtained from the National RNAi Core Facility in the Institute of Molecular Biology, Genomic Research Center, Academia Sinica. We are grateful to Andrew Bassett, Ruben Cauchi, Kay Davies, Stuart Grice, Hung-Fu Liao, Shau-Ping Lin, Todd Nystul, Chris Ponting, Priscilla Goldby and James Sleigh for their comments on this manuscript. This study was supported by the National Science Council, Taiwan, ROC (Grant Number 97-2313-B-002-006-MY3 and NSC 100-2313-B-002-051-MY2) to LYS and UK Medical Research Council to JLL.

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Authors and Affiliations

  1. Institute of Biotechnology, National Taiwan University, No. 81, Chang-Xiang St., Da-an District, Taipei, 106, Taiwan, ROC

    Wei-Fang Chang, Chia-Chun Chang, Mong-Hsun Tsai, Shinn-Chih Wu, Winston T. K. Cheng & Li-Ying Sung

  2. Agricultural Biotechnology Research Center, Academia Sinica, Taipei, 115, Taiwan, ROC

    Li-Ying Sung

  3. Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor, MI, USA

    Jie Xu

  4. Department of Physiology, National Cheng Kung University Medical College, Tainan, 701, Taiwan, ROC

    Shang-Hsun Yang

  5. Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, 201, Taiwan, ROC

    Hsin-Yang Li

  6. Department of Life Science, National Taiwan Normal University, Taipei, 116, Taiwan, ROC

    Hsiu Mei Hsieh-Li

  7. Department of Animal Science and Biotechnology, Tunghai University, Taichung, Taiwan, ROC

    Winston T. K. Cheng

  8. Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK

    Ji-Long Liu

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  1. Wei-Fang Chang
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Chang, WF., Xu, J., Chang, CC. et al. SMN is required for the maintenance of embryonic stem cells and neuronal differentiation in mice. Brain Struct Funct 220, 1539–1553 (2015). https://doi.org/10.1007/s00429-014-0743-7

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