Κατεύθυνση Αναπαραγωγική-Αναγεννητική Ιατρική
Library of the School of Health Sciences

2023-06-08

2023

Vasilopoulou Antonia-Gerasimina

Νικόλαος Ανάγνου, Ομότιμος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Πέτρος Δρακάκης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Δέσποινα Μαυρογιάννη, Ε.ΔΙ.Π, Ιατρική Σχολή, ΕΚΠΑ

Μελέτη της επι-μεταγραφωμικής τροποποίησης m6A του mRNA σε φυσιολογικά και θαλασσαιμικά αρχέγονα αιμοποιητικά κύτταρα CD34+ διαφόρων πηγών

Greek

Study of the m6A mRNA modification in normal and thalassemic primitive hematopoietic cells CD34+ from various sources

β-thalassemia is one of the most common autosomal recessive disorders that causes major health problems and can lead to disability and/or death. The hallmark of the disease is the imbalance in the α/β-globin chain production, which leads to ineffective erythropoiesis due to maturation arrest and apoptosis of polychromatic erythroblasts. Despite the extensive knowledge of the molecular defects involved in the pathophysiology of β-thalassemia, the underlying mechanisms that cause apoptosis are not yet fully elucidated. Also, interestingly, the clinical manifestations of the same genotype of thalassemia can be vastly different, likely due to epigenetic regulation. Over recent years, epitranscriptomic research provided a new layer of gene regulation during hematopoietic development and disease. N6-methyladenosine (m6A) is the most abundant in eukaryotic cells and plays a critical role in various biological processes that affect cell fate, including apoptosis and autophagy. This dynamic modification is regulated by methyltransferases, demethylases, and m6A-binding proteins. Emerging evidence suggests that m6A and its regulators are involved in every aspect of normal hematopoietic development, from hematopoietic stem cell emergence to the generation of mature blood cells. This raises the question of whether m6A RNA methylation and its regulators are implicated in the pathophysiology of thalassemic hematopoiesis.

In this study, the m6A RNA methylation pattern in normal and thalassemic hematopoiesis was investigated. To this extent, the expression profile of m6A enzymes was explored, using RT-qPCR, in hematopoietic stem cells CD34+ and proerythroblasts from peripheral blood of healthy donors and thalassemic individuals, as well as from umbilical cord blood of healthy newborns. Also, the m6A levels of total RNA were determined by an antibody-based colorimetric method. Finally, further analysis was performed to identify any gender-specific differences in the expression profile of these enzymes related to β-thalassemia. According to our findings, the m6A writers, readers, and erasers are differentially expressed in hematopoietic stem cells depending on both their source and stage of differentiation.
Importantly, we show that the transcriptional profile of these genes is altered in CD34+ cells of thalassemic patients compared to healthy donors. Lastly, our analysis revealed sex-dependent differentiation both in the relative expression of the m6A regulators and the m6A levels in erythroid precursors cells of patients with β-thalassemia.

Health Sciences

Beta-thalassemia, M6A RNA modification, Epitranscriptomics, Hematopoietic stem cells

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https://pergamos.lib.uoa.gr/uoa/dl/object/3301026