KLF2 regulates stemness of human mesenchymal stem cells by targeting FGFR3

ABSTRACT

Mesenchymal stem cells (MSCs) are an attractive source of pluripotent cells for regenerative therapy; however, maintaining stemness and self-renewal of MSCs during expansion ex vivo is challenging. For future clinical applications, it is essential to define the roles and signaling pathways that regulate the fate of MSCs. Based on our earlier finding that Krüppel-like factor 2 (KLF2) participates in maintaining stemness in MSCs, we examined further the role of this factor in intrinsic signaling pathways. Using a chromatin immunoprecipitation (ChIP)-sequence assay, we found that the FGFR3 gene is a KLF2 binding site. Knockdown of FGFR3 significantly decreased the levels of key pluripotency factors, enhanced the expression of differentiation-related genes and down-regulated colony formation of human bone marrow MSCs (hBMSCs). Using alizarin red S and oil red O staining, we found that knockdown of FGFR3 inhibited the osteogenic and adipogenic ability of MSCs under conditions of differentiation. The ChIP-qPCR assay confirmed that KLF2 interacts with the promoter regions of FGFR3. Our findings suggest that KLF2 promotes hBMSC stemness by direct regulation of FGFR. Our findings may contribute to enhanced MSC stemness by genetic modification of stemness-related genes.

KEYWORDS:

• FGFR3
• human
• KLF2
• mesenchymal stem cells
• stemness

Acknowledgments

Zhiyuan Gong and Zhanhao Shu contributed equally to this work. The English in this document was checked by two professional editors. For a certificate, see: http://www.textcheck.com/certificate/GzJnXE.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This investigation was supported financially by the National Natural Science Foundation of China [Grant no. 31570989.82100962] and by Zhejiang Provincial Natural Science Foundation of China [Grant no. LY15H140002, LQ21H140003].