SOX18-enforced expression diverts hemogenic endothelium-derived progenitors from T towards NK lymphoid pathways
1
Issued Date
2023-05-19
Resource Type
eISSN
25890042
Scopus ID
2-s2.0-85152950714
Journal Title
iScience
Volume
26
Issue
5
Rights Holder(s)
SCOPUS
Bibliographic Citation
iScience Vol.26 No.5 (2023)
Suggested Citation
Jung H.S., Suknuntha K., Kim Y.H., Liu P., Dettle S.T., Sedzro D.M., Smith P.R., Thomson J.A., Ong I.M., Slukvin I.I. SOX18-enforced expression diverts hemogenic endothelium-derived progenitors from T towards NK lymphoid pathways. iScience Vol.26 No.5 (2023). doi:10.1016/j.isci.2023.106621 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/82802
Title
SOX18-enforced expression diverts hemogenic endothelium-derived progenitors from T towards NK lymphoid pathways
Author's Affiliation
Other Contributor(s)
Abstract
Hemogenic endothelium (HE) is the main source of blood cells in the embryo. To improve blood manufacturing from human pluripotent stem cells (hPSCs), it is essential to define the molecular determinants that enhance HE specification and promote development of the desired blood lineage from HE. Here, using SOX18-inducible hPSCs, we revealed that SOX18 forced expression at the mesodermal stage, in contrast to its homolog SOX17, has minimal effects on arterial specification of HE, expression of HOXA genes and lymphoid differentiation. However, forced expression of SOX18 in HE during endothelial-to-hematopoietic transition (EHT) greatly increases NK versus T cell lineage commitment of hematopoietic progenitors (HPs) arising from HE predominantly expanding CD34+CD43+CD235a/CD41a−CD45− multipotent HPs and altering the expression of genes related to T cell and Toll-like receptor signaling. These studies improve our understanding of lymphoid cell specification during EHT and provide a new tool for enhancing NK cell production from hPSCs for immunotherapies.