Notch pathway in differentiation of human mesenchimal stem cells

Abstract

Notch is a key pathway in cell-cell communication and determining cell fate. Tissue-specific role of this signaling pathway is poorly understood. The purpose of this study was to investigate the influence of Notch pathway activation on adipogenic and osteogenic differentiation of mesenchimal stem cells (MSC) of human adipose tissue. Using lentiviral transduction we introduced activated intracellular domain of Notch1(NICD) into MSC and induced osteogenic and adipogenic differentiation. Introduction of NICD led to the activation of Notch target genes, HEY1 and HES1, both in differentiated and undifferentiated cells. Simultaneous exposure to activated NICD domain and differentiation inducers led to the block of both types of differentiation. The expression of specific markers was substantially decreased: PPARG and adipsin in adipogenic differentiation, and SPP1, IBSP, BGLAP in osteogenic differentiation. Thus, according to our data, induction of adipogenic and osteogenic differentiation in MSC associated with activation of Notch signaling pathway. At the same time, high nonspecific activation of the pathway prevented the differentiation of both types. The observed effect suggests that Notch pathway is involved in maintaining the balance between stemness and differentiation capacity of MSC. Refs 31. Figs 4. Tables 1.

Keywords:

Notch signaling, osteogenic differentiation, adipogenic differentiation, multipotent mesenchymal stromal cells