Abstract

The limited number of human hematopoietic stem cells (HSCs) has restrained their widespread clinical application. Despite great efforts in recent years, the in vitro expansion of HSCs remains a challenge due to incomplete understanding of the signaling networks underlying HSC self-renewal. Here, we show that culturing human cord blood (CB) CD34 + cells with JNK-IN-8, an inhibitor of the JNK signaling pathway, can enhance the self-renewal of HSCs with a 3.88-fold increase in cell number. These cultured CD34 + cells repopulated recipient mice for 21 weeks and can form secondary engraftment that lasted for more than 21 weeks. Knockdown of c-Jun , a major downstream target in the JNK pathway, promoted the expansion of hematopoietic stem and progenitor cells (HSPCs). Our findings demonstrate a critical role of the JNK pathway in regulating HSC expansion, provide new insights into HSC self-renewal mechanism, and may lead to improved clinical application of HSCs.