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Human induced pluripotent stem cell derived erythroblasts can undergo definitive erythropoiesis and co‐express gamma and beta globins
Author(s) -
Yang ChengTao,
French Anna,
Goh Pollyanna Agnes,
Pagnamenta Alistair,
Mettananda Sachith,
Taylor Jenny,
Knight Sam,
Nathwani Amit,
Roberts David J.,
Watt Suzanne M.,
Carpenter Lee
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12910
Subject(s) - erythropoiesis , induced pluripotent stem cell , globin , beta (programming language) , stem cell , hemoglobinopathy , microbiology and biotechnology , biology , cancer research , chemistry , immunology , embryonic stem cell , hemoglobin , genetics , medicine , anemia , gene , hemolytic anemia , biochemistry , computer science , programming language
Summary Human induced pluripotent stem cells (hi PSC s), like embryonic stem cells, are under intense investigation for novel approaches to model disease and for regenerative therapies. Here, we describe the derivation and characterization of hi PSC s from a variety of sources and show that, irrespective of origin or method of reprogramming, hi PSC s can be differentiated on OP 9 stroma towards a multi‐lineage haemo‐endothelial progenitor that can contribute to CD 144 + endothelium, CD 235a + erythrocytes (myeloid lineage) and CD 19 + B lymphocytes (lymphoid lineage). Within the erythroblast lineage, we were able to demonstrate by single cell analysis (flow cytometry), that hi PSC ‐derived erythroblasts express alpha globin as previously described, and that a sub‐population of these erythroblasts also express haemoglobin F (HbF), indicative of fetal definitive erythropoiesis. More notably however, we were able to demonstrate that a small sub‐fraction of HbF positive erythroblasts co‐expressed HbA in a highly heterogeneous manner, but analogous to cord blood‐derived erythroblasts when cultured using similar methods. Moreover, the HbA expressing erythroblast population could be greatly enhanced (44·0 ± 6·04%) when a defined serum‐free approach was employed to isolate a CD 31 + CD 45 + erythro‐myeloid progenitor. These findings demonstrate that hi PSC s may represent a useful alternative to standard sources of erythrocytes ( RBC s) for future applications in transfusion medicine.