title: Generation of functional erythrocytes from human embryonic stem cell-derived definitive hematopoiesis.
abstract: A critical issue for clinical utilization of human ES cells (hESCs) is whether they can generate terminally mature progenies with normal function. We recently developed a method for efficient production of hematopoietic progenitors from hESCs by coculture with murine fetal liver-derived stromal cells. Large numbers of hESCs-derived erythroid progenitors generated by the coculture enabled us to analyze the development of erythropoiesis at a clone level and investigate their function. The results showed that the globin expression in the erythroid cells in individual clones changed in a time-dependent manner. In particular, embryonic epsilon-globin-expressing erythroid cells from individual clones decreased, whereas adult-type beta-globin-expressing cells increased to approximately 100% in all clones we examined, indicating that the cells undergo definitive hematopoiesis. Enucleated erythrocytes also appeared among the clonal progeny. A comparison analysis showed that hESC-derived erythroid cells took a similar differentiation pathway to human cord blood CD34(+) progenitor-derived cells when examined for the expression of glycophorin A, CD71 and CD81. Furthermore, these hESC-derived erythroid cells could function as oxygen carriers and had a sufficient glucose-6-phosphate dehydrogenase activity. The present study should provide an experimental model for exploring early development of human erythropoiesis and hemoglobin switching and may help in the discovery of drugs for hereditary diseases in erythrocyte development.
authors.affiliation: Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Feng
authors.initials: F
authors.lastname: Ma
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ebihara
authors.forename: Katsutsugu
authors.initials: K
authors.lastname: Umeda
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sakai
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Hanada
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Yuji
authors.initials: Y
authors.lastname: Zaike
authors.forename: Eishun
authors.initials: E
authors.lastname: Tsuchida
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
authors.forename: Kohichiro
authors.initials: K
authors.lastname: Tsuji