Generation of functional erythrocytes from human embryonic stem cell-derived definitive hematopoiesis | Zendy

Feng Ma | Zendy; Yasuhiro Ebihara | Zendy; Katsutsugu Umeda | Zendy; Hiromi Sakai | Zendy; Sachiyo Hanada | Zendy; Hong Zhang | Zendy; Yuji Zaike | Zendy; Eishun Tsuchida | Zendy; Tatsutoshi Nakahata | Zendy; Hiromitsu Nakauchi | Zendy; Kohichiro Tsuji | Zendy

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Generation of functional erythrocytes from human embryonic stem cell-derived definitive hematopoiesis

Author(s) -

Feng Ma,

Yasuhiro Ebihara,

Katsutsugu Umeda,

Hiromi Sakai,

Sachiyo Hanada,

Hong Zhang,

Yuji Zaike,

Eishun Tsuchida,

Tatsutoshi Nakahata,

Hiromitsu Nakauchi,

Kohichiro Tsuji

Publication year - 2008

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.011

H-Index - 771

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.0802220105

Subject(s) - biology , haematopoiesis , erythropoiesis , embryonic stem cell , microbiology and biotechnology , stem cell , glycophorin , cord blood , progenitor cell , clone (java method) , fetal hemoglobin , cd34 , gata2 , immunology , fetus , genetics , gene , antigen , anemia , medicine , pregnancy

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.

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