
AsianScientist (Nov. 8, 2017) – In a study published in the British Journal of Haematology, scientists in Singapore have uncovered the molecular mechanism by which red blood cells mature.
Red blood cells are formed in the bone marrow from hematopoietic stem cells via a complex process known as erythropoiesis. Towards the end of this process, immature red blood cells known as reticulocytes, which are multi-lobular and spherical, undergo dynamic re-arrangements to yield highly deformable biconcave erythrocytes. Erythrocytes perform gaseous and nutrient exchange throughout the body. However, the molecular mechanisms underpinning these remarkable morphological and bio-mechanical transformations remained largely unknown.
In this study, a research team lead by Singapore University of Technology and Design (SUTD) Assistant Professor Rajesh Chandramohanadas used quantitative profiling of protein composition and imaging to explain how red blood cells mature.
Reticulocytes form a small proportion of human peripheral blood, often less than two percent of the total red blood cell population. Therefore, it is difficult to purify them in sufficient quantities and quality for large-scale experiments. To circumvent this problem, the researchers purified young reticulocytes from cord blood which contains approximately four percent of reticulocytes.
A magnetic selection protocol using an antibody against the transferrin receptor, a protein found on the surface of reticulocytes, was used to isolate the immature red blood cells. To reduce sample complexity and increase overall coverage, these cells were further sorted into membrane and soluble samples.
Thereafter, a quantitative mass spectrometry technique was used to identify and quantify of more than 1,800 proteins. This is by far the most comprehensive information on protein composition for human red blood cells.
The team carefully analyzed this large dataset and shortlisted certain proteins such as talin and tubulin, which dramatically changed between immature and mature blood cells. Although such proteins are known to confer stiffness to biological cells, they were confirmed as residues that remained in the reticulocytes.
The researchers then looked at the abundance of other proteins that are responsible for maintaining cellular architecture, such as a group of proteins called spectrins. Although the overall amount of spectrins remained comparable between reticulocytes and mature blood cells, the arrangement of these proteins were drastically different in reticulocytes. Filaments that formed the spectrin-based network shrunk by roughly 20 percent during maturation, and this could account for the transition in shape and deformability of reticulocytes.
“This robust dataset on the protein composition of human red blood cells could help promote understanding of pathological conditions that affect blood cell maturation and function,” said Chandramohanadas. “Furthermore, these results will facilitate targeted analysis of interactions between blood cells and infectious agents, such as Plasmodium vivax malaria parasites, which only infect young human reticulocytes.”
The article can be found at: Chu et al. (2017) Quantitative Mass Spectrometry of Human Reticulocytes Reveal Proteome-wide Modifications During Maturation.
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Source: Singapore University of Technology and Design.
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