Induced neural progenitor cells abundantly secrete extracellular vesicles and promote the proliferation of neural progenitors via extracellular signal–regulated kinase pathways

Abstract

Neural stem/progenitor cells (NPCs) are known to have potent therapeutic effects in neurological disorders through the secretion of extracellular vesicles (EVs). Despite the therapeutic potentials, the numbers of NPCs are limited in the brain, curbing the further use of EVs in the disease treatment. To overcome the limitation of NPC numbers, we used a three transcription factor (Brn2, Sox2, and Foxg1) somatic reprogramming approach to generate induced NPCs (iNPCs) from mouse fibroblasts and astrocytes. The resulting iNPCs released significantly higher numbers of EVs compared with wild-type NPCs (WT-NPCs). Furthermore, iNPCs-derived EVs (iNPC-EVs) promoted NPC function by increasing the proliferative potentials of WT-NPCs. Characterizations of EV contents through proteomics analysis revealed that iNPC-EVs contained higher levels of growth factor-associated proteins that were predicted to activate the downstream extracellular signal-regulated kinase (ERK) pathways. As expected, the proliferative effects of iNPC-derived EVs on WT-NPCs can be blocked by an ERK pathway inhibitor. Our data suggest potent therapeutic effects of iNPC-derived EVs through the promotion of NPC proliferation, release of growth factors, and activation of ERK pathways. These studies will help develop highly efficient cell-free therapeutic strategies for the treatment of neurological diseases.

Glutaminase C Regulates Microglial Activation and Pro-inflammatory Exosome Release: Relevance to the Pathogenesis of Alzheimer’s Disease

“…Immunochemistry was done as previously described (Ma et al, 2019). Briefly, cells or tissue sections were fixed in 4% paraformaldehyde (Sigma) for 15 min at room temperature (RT), washed 3 times with PBS (Thermo Fisher Scientific), and incubated with permeabilizing and blocking buffer containing 5% goat serum (Vector Laboratories) and 0.2% Triton X-100 (Bio-Rad) in PBS for 1 h at RT.…”

Comparative proteomic analysis reveals that exogenous 6-benzyladenine (6-BA) improves the defense system activity of waterlogged summer maize

“…Carbamidomethyl on Cys and oxidation on Met (or Acetylation on the Nterminal) were specified as fixed modification and variable modifications, respectively. False discovery rate (FDR) was set < 1% and minimum score for peptides was set > 40 to assess the confidence of the peptides [80]. TMT 10-plex was used in Mascot to quantify identified proteins.…”

Glutaminase 1 Regulates Neuroinflammation After Cerebral Ischemia Through Enhancing Microglial Activation and Pro-Inflammatory Exosome Release

“…Immunocytochemistry was done as previously described (13). Briefly, tissue sections were fixed in 4% paraformaldehyde (Sigma) for 15 min at room temperature (RT), washed 3 times with PBS (Fisher), and incubated with permeabilizing and blocking buffer containing 5% goat serum (Vector Laboratories) and 0.2% Triton X-100 (Bio-Rad) in PBS for 1 h at RT.…”