Journal
CURRENT MOLECULAR MEDICINE
Volume 16, Issue 8, Pages 738-746Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1566524016666160829153453
Keywords
mNPCs; cell cycle; CyclinD1; proliferation; anti-apoptosis
Categories
Funding
- National Basic Research Program of China (973 Program) [2014CB965001]
- National Natural Science Foundation of China Innovative Research Groups of the National Natural Science Foundation of China [81221001]
- Joint Research Fund for Overseas Chinese, Hong Kong and Macao Young Scientists of the National Natural Science Foundation of China [81329002]
- National Institutes of Health [R01 NS41858-01, 2R56NS041858-15A1, R03 NS094071-01]
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Background: Cell cycle regulation of neural progenitor cells (NPCs) is an essential process for neurogenesis, neural development, and repair after brain trauma. Stromal cell-derived factor-1 (SDF-1, CXCL12) and its receptors CXCR4 and CXCR7 are well known in regulating the migration and survival of NPCs. The effects of CXCL12 on NPCs proliferation, cell cycle regulation, and their associated signaling pathways remain unclear. Cyclin D1 is a protein required for progression through the G1 phase of the cell cycle and a known downstream target of beta-catenin. Therefore, cyclin D1 plays critical roles of cell cycle regulation, proliferation, and survival in NPCs. Methods: Primary mouse NPCs (mNPCs) were derived from brain tissues of wild-type, Cxcr4 knockout, or Cxcr7 knockout mice at mouse embryonic day 13.5 (E13.5). Flow cytometry was used to perform cell cycle analysis by quantitation of DNA content. Real-time PCR and Western blot were used to evaluate mRNA and protein expressions, respectively. Ki67 immunostaining and TUNEL assay were used to assess the proliferation and survival of mNPCs, respectively. Results: CXCL12 pretreatment led to the shortening of G0/G1 phase and lengthening of S phase, suggesting that CXCL12 regulates cell cycle progression in mNPCs. Consistently, CXCL12 treatment increased the expression of CyclinD1 and beta-catenin, and promoted proliferation and survival of mNPCs. Cxcr7 knockout of mNPCs blocked CXCL12-mediated mNPCs proliferation, whereas Cxcr4 knockout mNPC did not significantly effect CXCL12-mediated mNPCs proliferation. Conclusion: CXCR7 plays an important role in CXCL12-mediated mNPC cell cycle regulation and proliferation.
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