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The genomic analysis of erythrocyte microRNA expression in sickle cell diseases.
Abstract
BACKGROUND: Since mature erythrocytes are terminally differentiated cells without
nuclei and organelles, it is commonly thought that they do not contain nucleic acids.
In this study, we have re-examined this issue by analyzing the transcriptome of a
purified population of human mature erythrocytes from individuals with normal hemoglobin
(HbAA) and homozygous sickle cell disease (HbSS). METHODS AND FINDINGS: Using a combination
of microarray analysis, real-time RT-PCR and Northern blots, we found that mature
erythrocytes, while lacking ribosomal and large-sized RNAs, contain abundant and diverse
microRNAs. MicroRNA expression of erythrocytes was different from that of reticulocytes
and leukocytes, and contributed the majority of the microRNA expression in whole blood.
When we used microRNA microarrays to analyze erythrocytes from HbAA and HbSS individuals,
we noted a dramatic difference in their microRNA expression pattern. We found that
miR-320 played an important role for the down-regulation of its target gene, CD71
during reticulocyte terminal differentiation. Further investigation revealed that
poor expression of miR-320 in HbSS cells was associated with their defective downregulation
CD71 during terminal differentiation. CONCLUSIONS: In summary, we have discovered
significant microRNA expression in human mature erythrocytes, which is dramatically
altered in HbSS erythrocytes and their defect in terminal differentiation. Thus, the
global analysis of microRNA expression in circulating erythrocytes can provide mechanistic
insights into the disease phenotypes of erythrocyte diseases.
Type
Journal articleSubject
Anemia, Sickle CellAntigens, CD
Base Sequence
Blotting, Northern
DNA Primers
Erythrocytes
Gene Expression Profiling
Genomics
Hemoglobin, Sickle
Humans
MicroRNAs
Oligonucleotide Array Sequence Analysis
Phenotype
Receptors, Transferrin
Reverse Transcriptase Polymerase Chain Reaction
Permalink
https://hdl.handle.net/10161/4495Published Version (Please cite this version)
10.1371/journal.pone.0002360Publication Info
Chen, Shao-Yin; Wang, Yulei; Telen, Marilyn J; & Chi, Jen-Tsan (2008). The genomic analysis of erythrocyte microRNA expression in sickle cell diseases. PLoS One, 3(6). pp. e2360. 10.1371/journal.pone.0002360. Retrieved from https://hdl.handle.net/10161/4495.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Jen-Tsan Ashley Chi
Professor in Molecular Genetics and Mirobiology
We are using functional genomic approaches to investigate the nutrient signaling and
stress adaptations of cancer cells when exposed to various nutrient deprivations and
microenvironmental stress conditions. Recently, we focus on two areas. First, we are
elucidating the genetic determinants and disease relevance of ferroptosis, a newly
recognized form of cell death. Second, we have identified the mammalian stringent
response pathway which is highly similar to bacterial stringent response, but
Marilyn Jo Telen
Wellcome Clinical Distinguished Professor of Medicine in Honor of R. Wayne Rundles,
M.D.
Dr. Telen is recognized as an expert in the biochemistry and molecular genetics of
blood group antigens and the pathophysiological mechanisms of vaso-occlusion in sickle
cell disease. She is the Director of the Duke Comprehensive Sickle Cell Center. Dr.
Telen's laboratory focuses on structure/function analysis of membrane proteins expressed
by erythroid cells, as well as the role of these proteins in non-erythroid cells.
Proteins are also studied in transfectant systems, and researc
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