TY - JOUR
T1 - T Lymphocyte Potential Marks the Emergence of Definitive Hematopoietic Progenitors in Human Pluripotent Stem Cell Differentiation Cultures
AU - Kennedy, Marion
AU - Awong, Geneve
AU - Sturgeon, Christopher M.
AU - Ditadi, Andrea
AU - LaMotte-Mohs, Ross
AU - Zúñiga-Pflücker, Juan Carlos
AU - Keller, Gordon
N1 - Funding Information:
We would like to thank the members of the SickKids-UHN Flow Cytometry Facility for their expert assistance with cell sorting. This work was supported by National Institutes of Health grants U01 HL100395 and CIHR MOP93569 to G.K. and grants of the Canadian Institutes of Health Research (HOP83070; MOP12927), the Ontario HIV Treatment Network (OHTN), the Terry Fox Foundation, and the Krembil Foundation to J.C.Z.-P. A.D. and C.M.S. were supported by the Magna-Golftown Postdoctoral Fellowship and McMurrich Postdoctoral Fellowship, respectively, at the McEwen Centre for Regenerative Medicine, Toronto. G.A. was supported by a studentship from the OHTN.
PY - 2012/12/27
Y1 - 2012/12/27
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84871698997
U2 - 10.1016/j.celrep.2012.11.003
DO - 10.1016/j.celrep.2012.11.003
M3 - Article
C2 - 23219550
AN - SCOPUS:84871698997
SN - 2211-1247
VL - 2
SP - 1722
EP - 1735
JO - Cell Reports
JF - Cell Reports
IS - 6
ER -