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Comprehensive Characterization and Global Transcriptome Analysis of Human Fetal Liver terminal erythropoiesis

Genomics, Proteomics & Bioinformatics 2023年第6期21卷 1117-1132页

作者： Yongshuai Han Shihui Wang Yaomei Wang Yumin Huang Chengjie Gao Xinhua Guo Lixiang Chen Huizhi Zhao Xiuli An School of Life Sciences Zhengzhou UniversityZhengzhou 450001China Laboratory of Membrane Biology New York Blood CenterNew YorkNY 10065USA Institute of Hematology People’s Hospital of Zhengzhou UniversityZhengzhou 450003China Department of Hematology the Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450000China Department of Hematology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450002China

The fetal liver(FL)is the key erythropoietic organ during fetal development,but knowledge on human FL erythropoiesis is very limited.In this study,we sorted primary erythroblasts from FL cells and performed RNA sequencing(RNA-seq)analyses.We found that temporal gene expression patterns reflected changes in function during primary human FL terminal erythropoiesis.Notably,the expression of genes enriched in proteolysis and autophagy was up-regulated in orthochromatic erythroblasts(OrthoEs),suggesting the involvement of these pathways in enucleation.We also performed RNA-seq of in vitro cultured erythroblasts derived from FL CD34+cells.Comparison of transcriptomes between the primary and cultured erythroblasts revealed significant differences,indicating impacts of the culture system on gene expression.Notably,the expression of lipid metabolism-related genes was increased in cultured erythroblasts.We further immortalized erythroid cell lines from FL and cord blood(CB)CD34+cells(FL-iEry and CB-iEry,respectively).FL-iEry and CB-iEry were immortalized at the proerythroblast stage and can be induced to differentiate into OrthoEs,but their enucleation ability was very low.Comparison of the transcriptomes between OrthoEs with and without enucleation capability revealed the down-regulation of pathways involved in chromatin organization and mitophagy in OrthoEs without enucleation capacity,indicating that defects in chromatin organization and mitophagy contribute to the inability of OrthoEs to enucleate.Additionally,the expression of HBE1,HBZ,and HBG2 was up-regulated in FL-iEry compared with CB-iEry,and such up-regulation was accompanied by down-regulated expression of BCL11A and up-regulated expression of LIN28B and IGF2BP1.Our study provides new insights into human FL erythropoiesis and rich resources for future studies.

关键词： Human fetal liver terminal erythropoiesis Transcriptome Immortalized erythroid cell line Enucleation

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