PD-1 is required to maintain stem cell properties in human dental pulp stem cells

Cell Death and Differentiation
Yao LiuSongtao Shi

Abstract

Programmed cell death-1 (PD-1) belongs to an inhibitory signaling pathway capable of maintaining central and peripheral immune tolerance. Blockage of PD-1 has been identified as a promising immunotherapeutic approach for cancer and chronic infectious diseases. However, it is unknown whether PD-1 pathway regulates stem cell function. It is generally believed that mesenchymal stem cells (MSCs) produce PD-1 ligand, but fail to express PD-1. In this study, we show that neural crest-derived MSCs from dental pulp (MSC-DP), but not MSCs from bone marrow, expressed PD-1. Knocking down PD-1 expression in MSC-DP results in a significantly reduced capacity for cell proliferation and accelerated multipotential differentiation. Mechanistically, we show that PD-1 regulates a SHP2/ERK/Notch cascade to maintain proliferation and a SHP2/ERK/β-catenin cascade to inhibit osteo-/odontogenic differentiation. This study indicates that PD-1 is a key surface molecule controlling cell proliferation and multipotential differentiation of MSC-DP. Through regulating PD-1/SHP2/ERK signaling, we can significantly improve the quality and quantity of culture-expanded MSC-DP for potential clinical therapies.

References

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Citations

Oct 30, 2018·Journal of Dental Research·B SuiY Jin
Dec 7, 2018·Journal of Cellular Physiology·Bagher FarhoodKeywan Mortezaee
Oct 15, 2018·Journal of Cellular Physiology·Masoud NajafiKeywan Mortezaee
May 10, 2019·Current Osteoporosis Reports·Daniel W Youngstrom, Kurt D Hankenson
Aug 28, 2020·Frontiers in Immunology·Siyu LiuShu Guo
Jan 6, 2021·Archives of Dermatological Research·Lijuan ZhouQinping Yang
Sep 21, 2020·Journal of Endodontics·Bingdong SuiSongtao Shi
Aug 28, 2021·International Journal of Molecular Sciences·Zhuo XieZhengmei Lin

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Methods Mentioned

BETA
Flow cytometry

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