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Ferric citrate and apo-transferrin enable erythroblast maturation with β-globin from hemogenic endothelium

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Author(s)
Soo-Been JeonHyebin KohA-Reum HanJieun KimSunghun LeeJae-Ho LeeSeung-Soon ImYoung-Sup YoonJong-Hee LeeJi Yoon Lee
Keimyung Author(s)
Im, Seung Soon
Department
Dept. of Physiology (생리학)
Journal Title
NPJ Regen Med
Issued Date
2023
Volume
8
Issue
1
Abstract
Red blood cell (RBC) generation from human pluripotent stem cells (PSCs) offers potential for innovative cell therapy in regenerative medicine as well as developmental studies. Ex vivo erythropoiesis from PSCs is currently limited by the low efficiency of functional RBCs with β-globin expression in culture systems. During induction of β-globin expression, the absence of a physiological microenvironment, such as a bone marrow niche, may impair cell maturation and lineage specification. Here, we describe a simple and reproducible culture system that can be used to generate erythroblasts with β-globin expression. We prepared a two-dimensional defined culture with ferric citrate treatment based on definitive hemogenic endothelium (HE). Floating erythroblasts derived from HE cells were primarily CD45+CD71+CD235a+ cells, and their number increased remarkably upon Fe treatment. Upon maturation, the erythroblasts cultured in the presence of ferric citrate showed high transcriptional levels of β-globin and enrichment of genes associated with heme synthesis and cell cycle regulation, indicating functionality. The rapid maturation of these erythroblasts into RBCs was observed when injected in vivo, suggesting the development of RBCs that were ready to grow. Hence, induction of β-globin expression may be explained by the effects of ferric citrate that promote cell maturation by binding with soluble transferrin and entering the cells.Taken together, upon treatment with Fe, erythroblasts showed advanced maturity with a high transcription of β-globin. These findings can help devise a stable protocol for the generation of clinically applicable RBCs.
Keimyung Author(s)(Kor)
임승순
Publisher
School of Medicine (의과대학)
Type
Article
ISSN
2057-3995
Source
https://www.nature.com/articles/s41536-023-00320-4
DOI
10.1038/s41536-023-00320-4
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/45284
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
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