A common bipotent progenitor generates the erythroid and megakaryocyte lineages in embryonic stem cell-derived primitive hematopoiesis.
The megakaryocytic (MK) and erythroid lineages are tightly associated during differentiation and are generated from a bipotent megakaryocyte-erythroid progenitor (MEP). In the mouse, a primitive MEP has been demonstrated in the yolk sac. In human, it is not known whether the primitive MK and erythroid lineages are generated from a common progenitor or independently. Using hematopoietic differentiation of human embryonic stem cells on the OP9 cell line, we identified a primitive MEP in a subset of cells coexpressing glycophorin A (GPA) and CD41 from day 9 to day 12 of coculturing. This MEP differentiates into primitive erythroid (GPA(+)CD41(-)) and MK (GPA(-)CD41(+)) lineages. In contrast to erythropoietin (EPO)-dependent definitive hematopoiesis, KIT was not detected during erythroid differentiation. A molecular signature for the commitment and differentiation toward both the erythroid and MK lineages was detected by assessing expression of transcription factors, thrombopoietin receptor (MPL) and erythropoietin receptor (EPOR). We showed an inverse correlation between FLI1 and both KLF1 and EPOR during primitive erythroid and MK differentiation, similar to definitive hematopoiesis. This novel MEP differentiation system may allow an in-depth exploration of the molecular bases of erythroid and MK commitment and differentiation.
Klimchenko
Olena
O
Inserm U790, Institut Gustave Roussy, Villejuif, France.
Mori
Marcella
M
Distefano
Antonio
A
Langlois
Thierry
T
Larbret
Frédéric
F
Lecluse
Yann
Y
Feraud
Olivier
O
Vainchenker
William
W
Norol
Françoise
F
Debili
Najet
N
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology*; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism; D006021:Glycophorins / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D051917:Leukosialin / Q000378:metabolism; D055015:Megakaryocyte-Erythroid Progenitor Cells / Q000378:metabolism / Q000502:physiology*; D008533:Megakaryocytes / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism
D018952:Antigens, CD34; D006021:Glycophorins; D051917:Leukosialin; D019038:Platelet Glycoprotein GPIb-IX Complex; D040201:Platelet Membrane Glycoprotein IIb