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Hemogenic Reprogramming of Human Fibroblasts by Enforced Expression of Transcription Factors
Published on: November 4, 2019
Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A
Vijay G Sankaran1, Tobias F Menne, Jian Xu
1Division of Hematology/Oncology, Children's Hospital Boston, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
Science (New York, N.Y.)
|December 6, 2008
Summary
BCL11A gene variants impact fetal hemoglobin (HbF) levels. Down-regulating BCL11A in adult cells boosts HbF, suggesting BCL11A as a therapeutic target for sickle cell disease and beta-thalassemia.
Area of Science:
- Genetics
- Molecular Biology
- Hematology
Background:
- Fetal hemoglobin (HbF) levels influence the severity of sickle cell disease and beta-thalassemia syndromes.
- Genetic studies link BCL11A gene variants to variations in HbF levels.
Purpose of the Study:
- To investigate BCL11A as a regulator of fetal hemoglobin (HbF) expression.
- To explore BCL11A's role in the beta-globin gene cluster.
Main Methods:
- Analyzing the association between BCL11A genotype and BCL11A expression levels.
- Examining the developmental expression pattern of BCL11A in erythroid cells.
- Down-regulating BCL11A expression in primary adult erythroid cells.
- Investigating BCL11A binding sites within the beta-globin gene cluster.
Main Results:
- A high-HbF BCL11A genotype correlated with reduced BCL11A expression.
- Full-length BCL11A expression is primarily observed in adult erythroid cells.
- Reducing BCL11A expression in adult erythroid cells resulted in significant HbF reactivation.
- BCL11A was found to bind to multiple sites in the beta-globin gene cluster.
Conclusions:
- BCL11A acts as a repressor of fetal hemoglobin (HbF) expression in adult erythroid cells.
- BCL11A is a direct regulator of the beta-globin gene cluster.
- BCL11A represents a promising therapeutic target for increasing HbF levels in beta-hemoglobinopathies.
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