{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T15:16:27Z","timestamp":1772723787427,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["Grant Number 106-2313-B-002-039-MY3 and 109-2313-B-002 -003 -MY2 to L. S., 106-2314-B-195-006-MY3 and 109-2314-B-195-011 to C. L. and 108-2811-B-002-526 and 109-2811-B-002-544 to W. C."],"award-info":[{"award-number":["Grant Number 106-2313-B-002-039-MY3 and 109-2313-B-002 -003 -MY2 to L. S., 106-2314-B-195-006-MY3 and 109-2314-B-195-011 to C. L. and 108-2811-B-002-526 and 109-2811-B-002-544 to W. C."]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Survival motor neuron (SMN) is ubiquitously expressed in many cell types and its encoding gene, survival motor neuron 1 gene (SMN1), is highly conserved in various species. SMN is involved in the assembly of RNA spliceosomes, which are important for pre-mRNA splicing. A severe neurogenic disease, spinal muscular atrophy (SMA), is caused by the loss or mutation of SMN1 that specifically occurred in humans. We previously reported that SMN plays roles in stem cell biology in addition to its roles in neuron development. In this study, we investigated whether SMN can improve the propagation of spermatogonia stem cells (SSCs) and facilitate the spermatogenesis process. In in vitro culture, SSCs obtained from SMA model mice showed decreased growth rate accompanied by significantly reduced expression of spermatogonia marker promyelocytic leukemia zinc finger (PLZF) compared to those from heterozygous and wild-type littermates; whereas SMN overexpressed SSCs showed enhanced cell proliferation and improved potency. In vivo, the superior ability of homing and complete performance in differentiating progeny was shown in SMN overexpressed SSCs in host seminiferous tubule of transplant experiments compared to control groups. To gain insights into the roles of SMN in clinical infertility, we derived human induced pluripotent stem cells (hiPSCs) from azoospermia patients (AZ-hiPSCs) and from healthy control (ct-hiPSCs). Despite the otherwise comparable levels of hallmark iPCS markers, lower expression level of SMN1 was found in AZ-hiPSCs compared with control hiPSCs during in vitro primordial germ cell like cells (PGCLCs) differentiation. On the other hand, overexpressing hSMN1 in AZ-hiPSCs led to increased level of pluripotent markers such as OCT4 and KLF4 during PGCLC differentiation. Our work reveal novel roles of SMN in mammalian spermatogenesis and suggest new therapeutic targets for azoospermia treatment.<\/jats:p>","DOI":"10.3390\/ijms22020661","type":"journal-article","created":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T11:36:11Z","timestamp":1610364971000},"page":"661","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effects of Survival Motor Neuron Protein on Germ Cell Development in Mouse and Human"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8754-5991","authenticated-orcid":false,"given":"Wei-Fang","family":"Chang","sequence":"first","affiliation":[{"name":"Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Peng","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Hsu","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9452-2878","authenticated-orcid":false,"given":"Jie","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan-Chieh","family":"Cho","sequence":"additional","affiliation":[{"name":"Animal Resource Center, National Taiwan University, Taipei 106, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiu-Mei","family":"Hsieh-Li","sequence":"additional","affiliation":[{"name":"Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4834-8554","authenticated-orcid":false,"given":"Ji-Long","family":"Liu","sequence":"additional","affiliation":[{"name":"MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK"},{"name":"School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5588-4139","authenticated-orcid":false,"given":"Chung-Hao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei 105, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1221-2476","authenticated-orcid":false,"given":"Li-Ying","family":"Sung","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan"},{"name":"Animal Resource Center, National Taiwan University, Taipei 106, Taiwan"},{"name":"Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1111\/j.2047-2927.2013.00110.x","article-title":"The prevalence of couple infertility in the United States from a male perspective: Evidence from a nationally representative sample","volume":"1","author":"Louis","year":"2013","journal-title":"Androl. 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