Differentiation of glutamatergic neurons from mouse embryonic stem cells requires raptor S6K signaling

Jen Hua Chuang, Li Chu Tung, Yi Yin, Yen-Shou Lin

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Although the mammalian target of rapamycin complex 1 (mTORC1) functions as an important signaling complex in many cellular processes, the role of mTORC1 in neurons derived from embryonic stem cells (ESCs) has been less explored. Here, using a modified protocol to differentiate mouse ESCs (mESCs) into almost uniform glutamatergic neurons, we explored the importance of raptor/mTORC1 in the differentiation of mESCs. Raptor gene-trap mESCs, and raptor-knockdown mESCs formed smaller-sized embryonic bodies than the wild type and failed to undergo neuronal differentiation. Treatment with 1. μM rapamycin starting at the point when neuronal precursors began to differentiate from mESCs caused the gradual loss of neurites, shrinkage of soma, and a decreased ratio of neurite length to cell number over 48 to 72. h of treatment. This change was accompanied by activation of caspase-3 and S6 kinase (S6K), but not 4E-binding protein 1 (4EBP1). Knockdown of raptor during neuronal differentiation from mESCs also resulted in gradual loss of neurites and shrinkage of cell bodies. Loss of neurite density resulting from rapamycin treatment could be reversed by overexpression of S6K T389E. Taken together, these data demonstrate that raptor/mTORC1/S6K plays a critical role in the differentiation and survival of neurons derived from mESCs.

Original languageEnglish
Pages (from-to)1117-1128
Number of pages12
JournalStem Cell Research
Volume11
Issue number3
DOIs
Publication statusPublished - 2013 Nov 1

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Raptors
Ribosomal Protein S6 Kinases
Neurites
Neurons
Sirolimus
Somatotypes
Carisoprodol
Embryonic Stem Cells
Caspase 3
Mouse Embryonic Stem Cells
Carrier Proteins
Cell Count
mechanistic target of rapamycin complex 1
Genes

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Cite this

Differentiation of glutamatergic neurons from mouse embryonic stem cells requires raptor S6K signaling. / Chuang, Jen Hua; Tung, Li Chu; Yin, Yi; Lin, Yen-Shou.

In: Stem Cell Research, Vol. 11, No. 3, 01.11.2013, p. 1117-1128.

Research output: Contribution to journalArticle

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