2. Academic Validation
  3. A phosphoproteomics study reveals a defined genetic program for neural lineage commitment of neural stem cells induced by olfactory ensheathing cell-conditioned medium

A phosphoproteomics study reveals a defined genetic program for neural lineage commitment of neural stem cells induced by olfactory ensheathing cell-conditioned medium

  • Pharmacol Res. 2021 Oct;172:105797. doi: 10.1016/j.phrs.2021.105797.
Lite Ge 1,  Cheng Zhang 2,  Huali Xie 3,  Yi Zhuo 4,  Chengfeng Xun 3,  Ping Chen 5,  Zhiping Hu 6,  Ming Lu 7
Affiliations

Affiliations

  • 1 The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410006, PR China; Department of Neurology, Second Xiangya Hospital, Central South University, Changsha 410011, PR China; Hunan Provincical Key Laboratory of Neurorestoratology, The Second Affiliated Hospital, Hunan Normal University, Changsha 410003, PR China.
  • 2 The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410006, PR China; Guangdong Provincial Key Laboratory of Biotechnology for Plant Development, School of Life Science, South China Normal University, Guangzhou 510631, PR China.
  • 3 The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410006, PR China.
  • 4 The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410006, PR China; Hunan Provincical Key Laboratory of Neurorestoratology, The Second Affiliated Hospital, Hunan Normal University, Changsha 410003, PR China.
  • 5 The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410006, PR China. Electronic address: [email protected].
  • 6 Department of Neurology, Second Xiangya Hospital, Central South University, Changsha 410011, PR China. Electronic address: [email protected].
  • 7 The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410006, PR China; Hunan Provincical Key Laboratory of Neurorestoratology, The Second Affiliated Hospital, Hunan Normal University, Changsha 410003, PR China. Electronic address: [email protected].
PMID: 34352399 DOI: 10.1016/j.phrs.2021.105797
Abstract

Since both Olfactory ensheathing cells (OECs) and neural stem cells (NSCs) have shown certain efficacy in the cellular therapy of nerve injury and disease, there have been a series of investigations in recent years looking at the co-culture of NSCs and OECs. Protein phosphorylation forms the basis for identifying a variety of cellular signaling pathways responsible for regulating the self-renewal and differentiation of NSCs induced by OECs. To better understand the signaling cascades in the early phases of OEC-induced NSC differentiation, changes in the NSC proteome and phosphoproteome during the first 24 h were determined using dimethyl labeling and TiO2 phosphorylation enrichment coupled with Liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 565 proteins and 2511 phosphorylation sites were identified. According to quantitative phosphoproteomics analyses of NSC differentiation induced by OECs during the first 12 and 24 h, it was speculated that there were at least two different signal waves: one peaking within 12 h after stimulation and the second upsurge after 24 h. In addition to understanding the dynamics of the proteome and phosphoproteome in the early stages of NSC differentiation, our analyses identified a key role of the TGF-β3 protein secreted by OECs, which may be an initiating factor that promotes differentiation of NSCs into neurons induced by OECs. These findings not only redemonstrated a OECs-based therapeutic strategy in cell therapy, but also added a node to the regulatory network for the neural lineage commitment of NSCs induced by OECs.

Keywords

Acetonitrile (PubChem CID:6342); Ammonium persulfate (PubChem CID: 62648); Differentiation; Dimethyl sulfoxide (PubChem CID: 679); Dithiothreitol (PubChem CID: 446094); Formic acid (PubChem CID: 284); Glycine (PubChem CID: 750); Iodoacetamide (PubChem CID: 3727); N,N,N′,N′-Tetra(o-methylbenzyl)ethylene diamine (PubChem CID: 86028064); Neural stem cells; Olfactory ensheathing cells; Phosphoproteome; Transforming growth factor β3; Tris-hydroxymethyl-methyl-ammonium (PubChem CID: 4468930); Urea (PubChem CID:1176).

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