Globin switches in yolk sac-like primitive and fetal-like definitive red blood cells produced from human embryonic stem cells

Caihong Qiu, Emmanuel N. Olivier, Michelle Velho, Eric E. Bouhassira

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

We have previously shown that coculture of human embryonic stem cells (hESCs) for 14 days with immortalized fetal hepatocytes yields CD34+ cells that can be expanded in serum-free liquid culture into large numbers of megaloblastic nucleated erythroblasts resembling yolk sac-derived cells. We show here that these primitive erythroblasts undergo a switch in hemoglobin (Hb) composition during late terminal erythroid maturation with the basophilic erythroblasts expressing predominantly Hb Gower I (ζ2ε2) and the orthochromatic erythroblasts hemoglobin Gower II (α2ε 2). This suggests that the switch from Hb Gower I to Hb Gower II, the first hemoglobin switch in humans is a maturation switch not a lineage switch. We also show that extending the coculture of the hESCs with immortalized fetal hepatocytes to 35 days yields CD34+ cells that differentiate into more developmentally mature, fetal liver-like erythroblasts, that are smaller, express mostly fetal hemoglobin, and can enucleate. We conclude that hESC-derived erythropoiesis closely mimics early human development because the first 2 human hemoglobin switches are recapitulated, and because yolk sac-like and fetal liver-like cells are sequentially produced. Development of a method that yields erythroid cells with an adult phenotype remains necessary, because the most mature cells that can be produced with current systems express less than 2% adult β-globin mRNA.

Original languageEnglish (US)
Pages (from-to)2400-2408
Number of pages9
JournalBlood
Volume111
Issue number4
DOIs
StatePublished - Feb 15 2008

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Erythroblasts
Yolk Sac
Globins
Stem cells
Blood
Erythrocytes
Cells
Switches
Hemoglobins
Coculture Techniques
Hepatocytes
Liver
Fetal Hemoglobin
Erythroid Cells
Erythropoiesis
Human Development
Human Embryonic Stem Cells
Phenotype
Messenger RNA
hemoglobin Gower

ASJC Scopus subject areas

  • Hematology

Cite this

Globin switches in yolk sac-like primitive and fetal-like definitive red blood cells produced from human embryonic stem cells. / Qiu, Caihong; Olivier, Emmanuel N.; Velho, Michelle; Bouhassira, Eric E.

In: Blood, Vol. 111, No. 4, 15.02.2008, p. 2400-2408.

Research output: Contribution to journalArticle

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