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Experimental & Molecular Medicine, 2020.52, 56-65, DOI: https://doi.org/http://doi.org/10.1038/s12276-019-0357-5.
BMP4 and perivascular cells promote hematopoietic differentiation of human pluripotent stem cells in a differentiation stage-specific manner
Suji Jeong, Borim An; Jung-Hyun Kim; Hyo-Won Han; Jung-Hyun Kim; Hye-Ryeon Heo; Kwon-Soo Ha; Eun-Taek han; Won Sun Park and Seok-Ho Hong
The efficient and reproducible derivation and maturation of multipotent hematopoietic progenitors from human pluripotent stem cells (hPSCs) requires the recapitulation of appropriate developmental stages and the microenvironment. Here, using serum-, xeno-, and feeder-free stepwise hematopoietic induction protocols, we showed that short-term and high-concentration treatment of hPSCs with bone morphogenetic protein 4 (BMP4) strongly promoted early mesoderm induction followed by increased hematopoietic commitment. This method reduced variations in hematopoietic differentiation among hPSC lines maintained under chemically defined Essential 8 medium compared to those maintained under less-defined mTeSR medium. We also found that perivascular niche cells (PVCs) significantly augmented the production of hematopoietic cells via paracrine signaling mechanisms only when they were present during the hematopoietic commitment phase. A protein array revealed 86 differentially expressed (>1.5-fold) secretion factors in PVC-conditioned medium compared with serum-free control medium, of which the transforming growth factor-β inducible gene H3 significantly increased the number of hematopoietic colony-forming colonies. Our data suggest that BMP4 and PVCs promote the hematopoietic differentiation of hPSCs in a differentiation stage-specific manner. This will increase our understanding of hematopoietic development and expedite the development of hPSC-derived blood products for therapeutic use.
- DOI: https://doi.org/http://doi.org/10.1038/s12276-019-0357-5.
- ISBN or ISSN: 1226-3613
- 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
- This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.