Cell–Cell Contact Mediates Gene Expression and Fate Choice of Human Neural Stem/Progenitor Cells

Abstract

Transplantation of Neural Stem/Progenitor Cells (NPCs) is a promising regenerative strategy to promote neural repair following injury and degeneration because of the ability of these cells to proliferate, migrate, and integrate with the host tissue. Precise in vitro control of NPC proliferation without compromising multipotency and differentiation ability is critical in stem cell maintenance. This idea was highlighted in recent clinical trials, where discrepancies in NPC culturing protocols produced inconsistent therapeutic benefits. Of note, cell density plays an important role in regulating the survival, proliferation, differentiation, and fate choice of stem cells. To determine the extent of variability produced by inconsistent culturing densities, the present study cultured human-induced pluripotent NPCs (hiPSC-NPCs) at either a low or high plating density. hiPSC-NPCs were then isolated for transcriptomic analysis or differentiation in vitro. Following sequencing analysis, genes involved in cell–cell contact-mediated pathways, including Hippo-signaling, NOTCH, and WNT were differentially expressed. Modulation of these pathways was highly associated with the regulation of pro-neuronal transcription factors, which were also upregulated in response to higher-density hiPSC-NPC culture. Moreover, higher plating density translated into a greater neuronal and less astrocytic differentiation in vitro. This study highlights the importance of precisely controlling culture conditions during the development of NPC transplantation therapies.

Adult tissue-specific stem cell interaction: novel technologies and research advances

“…Conversely, when enhanced EphB2-ephrin-B3 signaling contributes to the maintenance of the quiescent state of rNSCs. In contrast, intercellular contacts affect gene expression and fate determination in human-induced pluripotent neural stem/progenitor cells cultured in vitro ( McIntyre et al, 2022 ). Transcriptome analysis identified the differential expression of Notch and Wnt, further suggesting that Notch and Wnt are responsible for the neurogenic cell fate of neural stem/progenitor cells.…”