Qiu, C., Olivier, E. N., Velho, M. and Bouhassira, E. E. (2008) Globin switches in yolk sac-like primitive and fetal-like definitive red blood cells produced from human embryonic stem cells. Blood, 111(4), pp. 2400-2408. (doi: 10.1182/blood-2007-07-102087)
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Publisher's URL: http://dx.doi.org/10.1182/blood-2007-07-102087
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 (α2ϵ2). 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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Olivier, Dr Emmanuel |
| Authors: | Qiu, C., Olivier, E. N., Velho, M., and Bouhassira, E. E. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | Blood |
| Publisher: | American Society of Hematology |
| ISSN: | 0006-4971 |
| ISSN (Online): | 1528-0020 |
| Related URLs: |
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