Global transcriptome analysis for identification of interactions between coding and noncoding RNAs during human erythroid differentiation

Abstract

Studies on coding genes, miRNAs, and lncRNAs during erythroid development have been performed in recent years. However, analysis focusing on the integration of the three RNA types has yet to be done. In the present study, we compared the dynamics of coding genes, miRNA, and lncRNA expression profiles. To explore dynamic changes in erythropoiesis and potential mechanisms that control these changes in the transcriptome level, we took advantage of high throughput sequencing technologies to obtain transcriptome data from cord blood hematopoietic stem cells and the following four erythroid differentiation stages, as well as from mature red blood cells. Results indicated that lncRNAs were promising cell marker candidates for erythroid differentiation. Clustering analysis classified the differentially expressed genes into four subtypes that corresponded to dynamic changes during stemness maintenance, mid-differentiation, and maturation. Integrated analysis revealed that noncoding RNAs potentially participated in controlling blood cell maturation, and especially associated with heme metabolism and responses to oxygen species and DNA damage. These regulatory interactions were displayed in a comprehensive network, thereby inferring correlations between RNAs and their associated functions. These data provided a substantial resource for the study of normal erythropoiesis, which will permit further investigation and understanding of erythroid development and acquired erythroid disorders.

Keywords

erythroid differentiation / hematopoietic stem cell / RNA-seq / miRNA / lncRNA

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Acknowledgements

This research was supported by the National “Twelfth Five-Year” Plan for Science & Technology Support (No. 2013BAI01B09 to X.F.), National Natural Science Foundation of China (No. 31471115 to X.F., No. 31401160 to H.Q., No. 31201097 to J.X.), National Key Scientific Instrument and Equipment Development Projects of China (No. 2011YQ03013404 to X.F.), National High Technology Research and Development Program of China (Nos. 2015AA020101 and 2015AA020108), and State Key Laboratory of Experimental Hematology Pilot Project Grant (No. ZK13-05 to Z.Z.), National High Technology Research and Development Program of China (No. 2013AA020107 to X.P.), National Natural Science Foundation of China (No. 31301199 to X.Y., No. 31401260 to F.F.), Guangzhou Health Care and Cooperative Innovation Major Project (No. 201400000003 to X.P.), and Guangdong Major Scientific and Technological Project (No. 2013A022100005 to X.P.).

Compliance with ethics guidelines

Nan Ding, Jiafei Xi, Yanming Li, Xiaoyan Xie, Jian Shi, Zhaojun Zhang, Yanhua Li, Fang Fang, Sihan Wang, Wen Yue, Xuetao Pei, and Xiangdong Fang declare that they have no conflicts of interest related to this work. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

Electronic Supplementary Material Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s11684-016-0452-0 and is accessible for authorized users.

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2016 Higher Education Press and Springer-Verlag Berlin Heidelberg