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Induction of adult levels of β-globin in human erythroid cells that intrinsically express embryonic or fetal globin by transduction with KLF1 and BCL11A-XL.
- Source :
-
Haematologica [Haematologica] 2014 Nov; Vol. 99 (11), pp. 1677-85. Date of Electronic Publication: 2014 Aug 08. - Publication Year :
- 2014
-
Abstract
- A major barrier to the clinical use of erythrocytes generated in vitro from pluripotent stem cells or cord blood progenitors is failure of these erythrocytes to express adult hemoglobin. The key regulators of globin switching KLF1 and BCL11A are absent or at a lower level than in adult cells in K562 and erythroid cells differentiated in vitro from induced pluripotent stem cells and cord blood progenitors. Transfection or transduction of K562 and cord blood erythroid cells with either KLF1 or BCL11A-XL had little effect on β-globin expression. In contrast, transduction with both transcription factors stimulated β-globin expression. Similarly, increasing the level of BCL11A-XL in the induced pluripotent stem cell-derived erythroid cell line HiDEP-1, which has levels of endogenous KLF1 similar to adult cells but lacks BCL11A, resulted in levels of β-globin equivalent to that of adult erythroid cells. Interestingly, this increase in β-globin was coincident with a decrease in ε- and ζ-, but not γ-globin, implicating BCL11A in repression of embryonic globin expression. The data show that KLF1 and BCL11A-XL together are required, but sufficient to induce adult levels of β-globin in induced pluripotent stem cell and cord blood-derived erythroid cells that intrinsically express embryonic or fetal globin.<br /> (Copyright© Ferrata Storti Foundation.)
- Subjects :
- Adult Stem Cells cytology
Adult Stem Cells metabolism
Cell Differentiation genetics
Cell Line
Erythroid Cells cytology
Hematopoietic Stem Cells cytology
Hematopoietic Stem Cells metabolism
Humans
Induced Pluripotent Stem Cells cytology
Induced Pluripotent Stem Cells metabolism
K562 Cells
Phenotype
Repressor Proteins
Transfection
epsilon-Globins genetics
gamma-Globins genetics
Carrier Proteins genetics
Erythroid Cells metabolism
Fetal Hemoglobin genetics
Gene Expression
Kruppel-Like Transcription Factors genetics
Nuclear Proteins genetics
Transduction, Genetic
beta-Globins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1592-8721
- Volume :
- 99
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Haematologica
- Publication Type :
- Academic Journal
- Accession number :
- 25107887
- Full Text :
- https://doi.org/10.3324/haematol.2014.110155