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Effects of Survival Motor Neuron Protein on Germ Cell Development in Mouse and Human
2021-01
发表期刊INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (IF:4.9[JCR-2023],5.6[5-Year])
EISSN1422-0067
卷号22期号:2页码:#VALUE!
DOI10.3390/ijms22020661
摘要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.
关键词survival motor neuron spermatogenesis azoospermia
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收录类别SCI ; SCIE
语种英语
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
WOS类目Biochemistry & Molecular Biology ; Chemistry, Multidisciplinary
WOS记录号WOS:000611307000001
出版者MDPI
原始文献类型Article
引用统计
被引频次:6[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/125934
专题生命科学与技术学院_PI研究组_刘冀珑组
通讯作者Lu, Chung-Hao; Sung, Li-Ying
作者单位
1.Natl Taiwan Univ, Inst Biotechnol, Taipei 106, Taiwan;
2.Univ Michigan, Med Ctr, Ctr Adv Models Translat Sci & Therapeut, Ann Arbor, MI 48109 USA;
3.Natl Taiwan Univ, Anim Resource Ctr, Taipei 106, Taiwan;
4.Natl Taiwan Normal Univ, Dept Life Sci, Taipei 116, Taiwan;
5.Univ Oxford, Dept Physiol Anat & Genet, MRC Funct Genom Unit, Oxford OX1 3PT, England;
6.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China;
7.Mackay Mem Hosp, Dept Obstet & Gynecol, Taipei 105, Taiwan;
8.Acad Sinica, Agr Biotechnol Res Ctr, Taipei 115, Taiwan
推荐引用方式
GB/T 7714
Chang, Wei-Fang,Peng, Min,Hsu, Jing,et al. Effects of Survival Motor Neuron Protein on Germ Cell Development in Mouse and Human[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2021,22(2):#VALUE!.
APA Chang, Wei-Fang.,Peng, Min.,Hsu, Jing.,Xu, Jie.,Cho, Huan-Chieh.,...&Sung, Li-Ying.(2021).Effects of Survival Motor Neuron Protein on Germ Cell Development in Mouse and Human.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,22(2),#VALUE!.
MLA Chang, Wei-Fang,et al."Effects of Survival Motor Neuron Protein on Germ Cell Development in Mouse and Human".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 22.2(2021):#VALUE!.
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