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

Wei Fang Chang, Jie Xu, Chia Chun Chang, Shang Hsun Yang, Hsin Yang Li, Hsiu Mei Hsieh, Mong Hsun Tsai, Shinn Chih Wu, Winston T.K. Cheng, Ji Long Liu, Li Ying Sung

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1539-1553
Number of pages15
JournalBrain Structure and Function
Volume220
Issue number3
DOIs
Publication statusPublished - 2015 May 1

Fingerprint

Motor Neurons
Embryonic Stem Cells
Cell Differentiation
Maintenance
Spinal Muscular Atrophy
Pluripotent Stem Cells
Teratoma
Tretinoin
Cell Division
Drosophila
Vertebrates
Stem Cells
Cell Proliferation
Mortality

Keywords

  • ERK signaling
  • Embryonic stem cell (ESC)
  • Neuronal differentiation
  • Survival motor neuron (SMN)

ASJC Scopus subject areas

  • Anatomy
  • Neuroscience(all)
  • Histology

Cite this

SMN is required for the maintenance of embryonic stem cells and neuronal differentiation in mice. / Chang, Wei Fang; Xu, Jie; Chang, Chia Chun; Yang, Shang Hsun; Li, Hsin Yang; Hsieh, Hsiu Mei; Tsai, Mong Hsun; Wu, Shinn Chih; Cheng, Winston T.K.; Liu, Ji Long; Sung, Li Ying.

In: Brain Structure and Function, Vol. 220, No. 3, 01.05.2015, p. 1539-1553.

Research output: Contribution to journalArticle

Chang, WF, Xu, J, Chang, CC, Yang, SH, Li, HY, Hsieh, HM, Tsai, MH, Wu, SC, Cheng, WTK, Liu, JL & Sung, LY 2015, 'SMN is required for the maintenance of embryonic stem cells and neuronal differentiation in mice', Brain Structure and Function, vol. 220, no. 3, pp. 1539-1553. https://doi.org/10.1007/s00429-014-0743-7
Chang, Wei Fang ; Xu, Jie ; Chang, Chia Chun ; Yang, Shang Hsun ; Li, Hsin Yang ; Hsieh, Hsiu Mei ; Tsai, Mong Hsun ; Wu, Shinn Chih ; Cheng, Winston T.K. ; Liu, Ji Long ; Sung, Li Ying. / SMN is required for the maintenance of embryonic stem cells and neuronal differentiation in mice. In: Brain Structure and Function. 2015 ; Vol. 220, No. 3. pp. 1539-1553.
@article{75a6023c8e2f466a995b9a975260e19d,
title = "SMN is required for the maintenance of embryonic stem cells and neuronal differentiation in mice",
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.",
keywords = "ERK signaling, Embryonic stem cell (ESC), Neuronal differentiation, Survival motor neuron (SMN)",
author = "Chang, {Wei Fang} and Jie Xu and Chang, {Chia Chun} and Yang, {Shang Hsun} and Li, {Hsin Yang} and Hsieh, {Hsiu Mei} and Tsai, {Mong Hsun} and Wu, {Shinn Chih} and Cheng, {Winston T.K.} and Liu, {Ji Long} and Sung, {Li Ying}",
year = "2015",
month = "5",
day = "1",
doi = "10.1007/s00429-014-0743-7",
language = "English",
volume = "220",
pages = "1539--1553",
journal = "Brain Structure and Function",
issn = "1863-2653",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - SMN is required for the maintenance of embryonic stem cells and neuronal differentiation in mice

AU - Chang, Wei Fang

AU - Xu, Jie

AU - Chang, Chia Chun

AU - Yang, Shang Hsun

AU - Li, Hsin Yang

AU - Hsieh, Hsiu Mei

AU - Tsai, Mong Hsun

AU - Wu, Shinn Chih

AU - Cheng, Winston T.K.

AU - Liu, Ji Long

AU - Sung, Li Ying

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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.

AB - 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.

KW - ERK signaling

KW - Embryonic stem cell (ESC)

KW - Neuronal differentiation

KW - Survival motor neuron (SMN)

UR - http://www.scopus.com/inward/record.url?scp=84895931509&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84895931509&partnerID=8YFLogxK

U2 - 10.1007/s00429-014-0743-7

DO - 10.1007/s00429-014-0743-7

M3 - Article

C2 - 24633826

AN - SCOPUS:84895931509

VL - 220

SP - 1539

EP - 1553

JO - Brain Structure and Function

JF - Brain Structure and Function

SN - 1863-2653

IS - 3

ER -