title: T lymphocyte potential marks the emergence of definitive hematopoietic progenitors in human pluripotent stem cell differentiation cultures.
abstract: The efficient generation of hematopoietic stem cells from human pluripotent stem cells is dependent on the appropriate specification of the definitive hematopoietic program during differentiation. In this study, we used T lymphocyte potential to track the onset of definitive hematopoiesis from human embryonic and induced pluripotent stem cells differentiated with specific morphogens in serum- and stromal-free cultures. We show that this program develops from a progenitor population with characteristics of hemogenic endothelium, including the expression of CD34, VE-cadherin, GATA2, LMO2, and RUNX1. Along with T cells, these progenitors display the capacity to generate myeloid and erythroid cells. Manipulation of Activin/Nodal signaling during early stages of differentiation revealed that development of the definitive hematopoietic progenitor population is not dependent on this pathway, distinguishing it from primitive hematopoiesis. Collectively, these findings demonstrate that it is possible to generate T lymphoid progenitors from pluripotent stem cells and that this lineage develops from a population whose emergence marks the onset of human definitive hematopoiesis.
authors.affiliation: McEwen Centre for Regenerative Medicine, University Health Network, Toronto, Ontario, Canada.
authors.forename: Marion
authors.initials: M
authors.lastname: Kennedy
authors.forename: Geneve
authors.initials: G
authors.lastname: Awong
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Sturgeon
authors.forename: Andrea
authors.initials: A
authors.lastname: Ditadi
authors.forename: Ross
authors.initials: R
authors.lastname: LaMotte-Mohs
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Zúñiga-Pflücker
authors.forename: Gordon
authors.initials: G
authors.lastname: Keller
mesh_terms: D000943:Antigens, Differentiation / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation