人类胎儿肝脏末期红细胞生成的全面特征描述和全局转录组分析

IF 11.5 2区 生物学 Q1 GENETICS & HEREDITY
Genomics, Proteomics & Bioinformatics Pub Date : 2023-12-01 Epub Date: 2023-08-30 DOI:10.1016/j.gpb.2023.07.001
Yongshuai Han, Shihui Wang, Yaomei Wang, Yumin Huang, Chengjie Gao, Xinhua Guo, Lixiang Chen, Huizhi Zhao, Xiuli An
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引用次数: 0

摘要

胎儿肝脏(FL)是胎儿发育过程中关键的红细胞生成器官,但有关人类FL红细胞生成的知识却非常有限。在这项研究中,我们从FL细胞中分拣出原代红细胞,并进行了RNA测序(RNA-seq)分析。我们发现,时间基因表达模式反映了原代人类 FL 终末红细胞生成过程中的功能变化。值得注意的是,在正色红细胞(OrthoEs)中,富含蛋白分解和自噬的基因表达上调,这表明这些通路参与了去核过程。我们还对从FL CD34+细胞中提取的体外培养红细胞进行了RNA-seq分析。比较原代红细胞和培养红细胞的转录组发现了显著差异,表明培养系统对基因表达有影响。值得注意的是,脂质代谢相关基因的表达在培养红细胞中有所增加。我们进一步从 FL 和脐带血(CB)CD34+细胞中永生化了红细胞系(分别为 FL-iEry 和 CB-iEry)。FL-iEry和CB-iEry在原红细胞阶段永生,可诱导分化成OrthoEs,但它们的去核能力很低。比较具有和不具有去核能力的OrthoEs的转录组发现,在不具有去核能力的OrthoEs中,参与染色质组织和有丝分裂的通路下调,这表明染色质组织和有丝分裂的缺陷导致OrthoEs不能去核。此外,与 CB-iEry 相比,FL-iEry 中 HBE1、HBZ 和 HBG2 的表达上调,这种上调伴随着 BCL11A 的表达下调以及 LIN28B 和 IGF2BP1 的表达上调。我们的研究为人类 FL 红细胞生成提供了新的见解,并为今后的研究提供了丰富的资源。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comprehensive Characterization and Global Transcriptome Analysis of Human Fetal Liver Terminal Erythropoiesis.

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.

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来源期刊
Genomics, Proteomics & Bioinformatics
Genomics, Proteomics & Bioinformatics Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
14.30
自引率
4.20%
发文量
844
审稿时长
61 days
期刊介绍: Genomics, Proteomics and Bioinformatics (GPB) is the official journal of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China. It aims to disseminate new developments in the field of omics and bioinformatics, publish high-quality discoveries quickly, and promote open access and online publication. GPB welcomes submissions in all areas of life science, biology, and biomedicine, with a focus on large data acquisition, analysis, and curation. Manuscripts covering omics and related bioinformatics topics are particularly encouraged. GPB is indexed/abstracted by PubMed/MEDLINE, PubMed Central, Scopus, BIOSIS Previews, Chemical Abstracts, CSCD, among others.
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