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The globin switching of the in vitro hematopoietic differentiation

Grant number: 17/08057-2
Support type:Scholarships in Brazil - Master
Effective date (Start): January 01, 2018
Effective date (End): December 31, 2018
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Dimas Tadeu Covas
Grantee:Alexander Rodrigo Ferreira
Home Institution: Hemocentro de Ribeirão Preto. Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP (HCMRP). Secretaria da Saúde (São Paulo - Estado). Ribeirão Preto , SP, Brazil
Associated research grant:13/08135-2 - CTC - Center for Cell-Based Therapy, AP.CEPID

Abstract

In the course of human development, different sets of globins are successively expressed and result in different hemoglobin levels over time. However, the molecular mechanisms responsible for this globin switching process are still poorly understood and mutations in some globins genes may alter the morphological and functional characteristics of hemoglobins. Pluripotent stem cells can be used as an in vitro model for understanding the natural processes of human development, including the hematopoietic differentiation. Thus, it is necessary to characterize the normal or mutated levels of globins in cells obtained by this process, which will help in the comprehension of the mechanisms that induce changes in the globin profile, recapitulating the stages of human development. The main objective of this proposal to develop a proteomics method to quantitatively evaluate and distinguish the globins (±, ², ´, µ, ³, and ¶) profile throughout the in vitro hematopoietic differentiation process from pluripotent stem cells, creating more reproducible protocols. As a result, we intend to validate a robust, sensitive, and highly specific tool for the globins characterization and quantification and that can be applied in translational studies as a diagnostic tool for hemoglobinopathies, in the biomarkers detection, and as a model for erythropoiesis disorders.

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