SOX18-enforced expression diverts hemogenic endothelium-derived progenitors from T towards NK lymphoid pathways
Ho Sun Jung,
Kran Suknuntha,
Yun Hee Kim,
Peng Liu,
Samuel T. Dettle,
Divine Mensah Sedzro,
Portia R. Smith,
James A. Thomson,
Irene M. Ong,
Igor I. Slukvin
Affiliations
Ho Sun Jung
Wisconsin National Primate Research Center, University of Wisconsin Graduate School, 1220 Capitol Court, Madison, WI 53715, USA
Kran Suknuntha
Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, 600 Highland Avenue, Madison, WI 53792, USA; Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan 10540, Thailand
Yun Hee Kim
Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, 600 Highland Avenue, Madison, WI 53792, USA
Peng Liu
Departments of Statistics and of Biostatistics and Medical Informatics, Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA
Samuel T. Dettle
Wisconsin National Primate Research Center, University of Wisconsin Graduate School, 1220 Capitol Court, Madison, WI 53715, USA
Divine Mensah Sedzro
Wisconsin National Primate Research Center, University of Wisconsin Graduate School, 1220 Capitol Court, Madison, WI 53715, USA
Portia R. Smith
Wisconsin National Primate Research Center, University of Wisconsin Graduate School, 1220 Capitol Court, Madison, WI 53715, USA
James A. Thomson
Morgridge Institute for Research, 330 N. Orchard Street, Madison, WI 53715, USA; Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53707-7365, USA; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA
Irene M. Ong
Departments of Statistics and of Biostatistics and Medical Informatics, Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA
Igor I. Slukvin
Wisconsin National Primate Research Center, University of Wisconsin Graduate School, 1220 Capitol Court, Madison, WI 53715, USA; Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, 600 Highland Avenue, Madison, WI 53792, USA; Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53707-7365, USA; Corresponding author
Summary: 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.
