TY - JOUR
T1 - Survival Motor Neuron Enhances Pluripotent Gene Expression and Facilitates Cell Reprogramming
AU - Chang, Wei Fang
AU - Lin, Tzu Ying
AU - Peng, Min
AU - Chang, Chia Chun
AU - Xu, Jie
AU - Hsieh-Li, Hsiu Mei
AU - Liu, Ji Long
AU - Sung, Li Ying
N1 - Funding Information:
This research was funded by the Ministry of Science and Technology, Taiwan (MOST 106-2313-B-002-039-MY3, MOST 109-2313-B-002-003-MY2 to L.-Y.S., and MOST 110-2811-B-002-624 to W.-F.C.).
Publisher Copyright:
© Copyright 2022, Mary Ann Liebert, Inc., publishers 2022.
PY - 2022/11
Y1 - 2022/11
N2 - Survival motor neuron (SMN) plays important roles in snRNP assembly and mRNA splicing. Deficiency of SMN causes spinal muscular atrophy (SMA), a leading genetic disease causing childhood mortality. Previous studies have shown that SMN regulates stem cell self-renewal and pluripotency in Drosophila and mouse and is abundantly expressed in mouse embryonic stem cells. However, whether SMN is required for establishment of pluripotency is unclear. In this study, we show that SMN is gradually upregulated in preimplantation mouse embryos and cultured cells undergoing cell reprogramming. Ectopic expression of SMN increased cell reprogramming efficiency, whereas knockdown of SMN impeded induced pluripotent stem cell (iPSC) colony formation. iPSCs could be derived from SMA model mice, but impairment in differentiation capacity may be present. The ectopic overexpression of SMN in iPSCs can upregulate the expression levels of some pluripotent genes and restore the neuronal differentiation capacity of SMA-iPSCs. Taken together, our findings not only demonstrate the functional relevance of SMN in establishment of cell pluripotency but also propose its potential application in facilitating iPSC derivation.
AB - Survival motor neuron (SMN) plays important roles in snRNP assembly and mRNA splicing. Deficiency of SMN causes spinal muscular atrophy (SMA), a leading genetic disease causing childhood mortality. Previous studies have shown that SMN regulates stem cell self-renewal and pluripotency in Drosophila and mouse and is abundantly expressed in mouse embryonic stem cells. However, whether SMN is required for establishment of pluripotency is unclear. In this study, we show that SMN is gradually upregulated in preimplantation mouse embryos and cultured cells undergoing cell reprogramming. Ectopic expression of SMN increased cell reprogramming efficiency, whereas knockdown of SMN impeded induced pluripotent stem cell (iPSC) colony formation. iPSCs could be derived from SMA model mice, but impairment in differentiation capacity may be present. The ectopic overexpression of SMN in iPSCs can upregulate the expression levels of some pluripotent genes and restore the neuronal differentiation capacity of SMA-iPSCs. Taken together, our findings not only demonstrate the functional relevance of SMN in establishment of cell pluripotency but also propose its potential application in facilitating iPSC derivation.
KW - induced pluripotent stem cells
KW - neuronal differentiation
KW - somatic cell reprogramming
KW - spinal muscular atrophy
KW - survival motor neuron
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U2 - 10.1089/scd.2022.0091
DO - 10.1089/scd.2022.0091
M3 - Article
C2 - 35848514
AN - SCOPUS:85141893487
SN - 1547-3287
VL - 31
SP - 696
EP - 705
JO - Stem Cells and Development
JF - Stem Cells and Development
IS - 21-22
ER -