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Autonomous control of terminal erythropoiesis via physical interactions among erythroid cells

 Hye Sook Choi  ;  Eun Mi Lee  ;  HyunOkKim  ;  Moon-Il Park  ;  Eun Jung Ba다 
 STEM CELL RESEARCH, Vol.10(3) : 442-453, 2013 
Journal Title
Issue Date
Cell Adhesion Molecules/genetics ; Cell Adhesion Molecules/metabolism ; Cell Adhesion Molecules/pharmacology ; Cell Communication ; Cell Lineage ; Cells, Cultured ; Culture Media, Conditioned/pharmacology ; Cytokinesis ; Erythroblasts/cytology* ; Erythroblasts/metabolism ; Erythropoiesis/drug effects ; Fetal Blood/cytology ; GTPase-Activating Proteins/metabolism ; Humans ; K562 Cells ; Macrophages/cytology ; Macrophages/metabolism ; Protein Binding ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/genetics ; Recombinant Proteins/pharmacology ; Tumor Suppressor Proteins/metabolism
In vitro erythropoiesis has been studied extensively for its application in the manufacture of transfusable erythrocytes. Unfortunately, culture conditions have not been as effective as in vivo growth conditions, where bone marrow macrophages are known to be a key regulator of erythropoiesis. This study focused on the fact that some erythroblasts are detached from macrophages and only contact other erythroblasts. We hypothesized that additional factors regulate erythroblasts, likely through either physical contact or secreted factors. To further elucidate these critical factors, human erythroblasts derived from cord blood were cultured at high density to mimic marrow conditions. This growth condition resulted in a significantly increased erythroid enucleation rate and viability. We found several novel contact-related signals in erythroblasts: intercellular adhesion molecule-4 (ICAM-4) and deleted in liver cancer-1 (DLC-1). DLC-1, a Rho-GTPase-activating protein, has not previously been reported in erythroid cells, but its interaction with ICAM-4 was demonstrated here. We further confirmed the presence of a secreted form of human ICAM-4 for the first time. When soluble ICAM-4 was added to media, cell viability and enucleation increased with decreased nuclear dysplasia, suggesting that ICAM-4 is a key factor in contact between cells. These results highlight potential new mechanisms for autonomous control of erythropoiesis. The application of these procedures to erythrocyte manufacturing could enhance in vitro erythrocyte production for clinical use.
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1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyun Ok(김현옥) ORCID logo https://orcid.org/0000-0002-4964-1963
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