Role of YAP in hematopoietic differentiation and erythroid lineage specification of human-induced pluripotent stem cells
1
Issued Date
2023-09-29
Resource Type
eISSN
17576512
Scopus ID
2-s2.0-85172825041
Pubmed ID
37775798
Journal Title
Stem cell research & therapy
Volume
14
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Stem cell research & therapy Vol.14 No.1 (2023) , 279
Suggested Citation
Laowtammathron C., Lorthongpanich C., Jiamvoraphong N., Srisook P., Klaihmon P., Kheolamai P., Luanpitpong S., Issaragrisil S. Role of YAP in hematopoietic differentiation and erythroid lineage specification of human-induced pluripotent stem cells. Stem cell research & therapy Vol.14 No.1 (2023) , 279. doi:10.1186/s13287-023-03508-z Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/90350
Title
Role of YAP in hematopoietic differentiation and erythroid lineage specification of human-induced pluripotent stem cells
Author's Affiliation
Other Contributor(s)
Abstract
BACKGROUND: In vitro production of hematopoietic stem/progenitor cells (HSPCs) from human-induced pluripotent stem cells (hiPSCs) provides opportunities for fundamental research, disease modeling, and large-scale production of HLA-matched HSPCs for therapeutic applications. However, a comprehensive understanding of the signaling mechanisms that regulate human hematopoiesis is needed to develop a more effective procedure for deriving HSPCs from hiPSCs. METHODS: In this study, we investigate the role of YAP during the hematopoietic differentiation of hiPSCs to HSPCs and erythrocytes using the isogenic YAP-overexpressing (YAP-S5A) and YAP-depleting (YAP-KD) hiPSCs to eliminate the effects of a genetic background variation. RESULTS: Although YAP is dispensable for maintaining the self-renewal and pluripotency of these hiPSCs, it affects the early cell-fate determination and hematopoietic differentiation of hiPSCs. Depleting YAP enhances the derivation efficiency of HSPCs from hiPSCs by inducing the mesodermal lineage commitment, promoting hematopoietic differentiation, and preventing the differentiation toward endothelial lineage. On the contrary, the overexpression of YAP reduced HSPCs yield by inducing the endodermal lineage commitment, suppressing hematopoietic differentiation, and promoting the differentiation toward endothelial lineage. CONCLUSIONS: Expression of YAP is crucial for the differentiation of hiPSC-derived HSPCs toward mature erythrocytes. We believe that by manipulating YAP activity using small molecules, the efficiency of the large-scale in vitro production system for generating hematopoietic stem/progenitor cells for future therapeutic use could be improved.