Developmental transcriptome analysis of human erythropoiesis.
To globally survey the changes in transcriptional landscape during terminal erythroid differentiation, we performed RNA sequencing (RNA-seq) on primary human CD34(+) cells after ex vivo differentiation from the earliest into the most mature erythroid cell stages. This analysis identified thousands of novel intergenic and intronic transcripts as well as novel alternative transcript isoforms. After rigorous data filtering, 51 (presumptive) novel protein-coding transcripts, 5326 long and 679 small non-coding RNA candidates remained. The analysis also revealed two clear transcriptional trends during terminal erythroid differentiation: first, the complexity of transcript diversity was predominantly achieved by alternative splicing, and second, splicing junctional diversity diminished during erythroid differentiation. Finally, 404 genes that were not known previously to be differentially expressed in erythroid cells were annotated. Analysis of the most extremely differentially expressed transcripts revealed that these gene products were all closely associated with hematopoietic lineage differentiation. Taken together, this study will serve as a comprehensive platform for future in-depth investigation of human erythroid development that, in turn, may reveal new insights into multiple layers of the transcriptional regulatory hierarchy that controls erythropoiesis.
Department of Cell and Developmental Biology and.
Lihong
L
Shi
Department of Cell and Developmental Biology and Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Yu-Hsuan
YH
Lin
Department of Cell and Developmental Biology and.
M C
MC
Sierant
Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Fan
F
Zhu
Department of Cell and Developmental Biology and.
Shuaiying
S
Cui
Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Yuanfang
Y
Guan
Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Maureen A
MA
Sartor
Department of Cell and Developmental Biology and Department of Integrative Genomics, Tohoku Medical Megabank, Tohoku University, 2-1 Seiryo-machi, Sendai 980-8573, Japan.
Osamu
O
Tanabe
Department of Cell and Developmental Biology and.
Kim-Chew
KC
Lim
Department of Cell and Developmental Biology and engel@umich.edu.
James Douglas
JD
Engel
D000328:Adult; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism; D004920:Erythropoiesis / Q000235:genetics*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D016366:Open Reading Frames / Q000235:genetics; D020033:Protein Isoforms / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics; D017423:Sequence Analysis, RNA; D055544:beta-Globins / Q000378:metabolism
D020033:Protein Isoforms; D012333:RNA, Messenger; D022661:RNA, Untranslated; D055544:beta-Globins