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Article

Distinct miRNA Signatures and Networks Discern Fetal from Adult Erythroid Differentiation and Primary from Immortalized Erythroid Cells

1
Department of Molecular Genetics Thalassemia, The Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus
2
Cyprus School of Molecular Medicine, Nicosia 2371, Cyprus
3
Cell Engineering Division, RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan
4
Thalassemia Clinic Larnaca, Larnaca General Hospital, Larnaca 6301, Cyprus
5
Thalassemia Clinic Nicosia, Archbishop Makarios III Hospital, Nicosia 1474, Cyprus
*
Author to whom correspondence should be addressed.
Contributed equally to this work.
Academic Editor: Michał Dąbrowski
Int. J. Mol. Sci. 2021, 22(7), 3626; https://doi.org/10.3390/ijms22073626
Received: 15 February 2021 / Revised: 23 March 2021 / Accepted: 24 March 2021 / Published: 31 March 2021
(This article belongs to the Special Issue Functions of Non-coding DNA Regions)
MicroRNAs (miRNAs) are small non-coding RNAs crucial for post-transcriptional and translational regulation of cellular and developmental pathways. The study of miRNAs in erythropoiesis elucidates underlying regulatory mechanisms and facilitates related diagnostic and therapy development. Here, we used DNA Nanoball (DNB) small RNA sequencing to comprehensively characterize miRNAs in human erythroid cell cultures. Based on primary human peripheral-blood-derived CD34+ (hCD34+) cells and two influential erythroid cell lines with adult and fetal hemoglobin expression patterns, HUDEP-2 and HUDEP-1, respectively, our study links differential miRNA expression to erythroid differentiation, cell type, and hemoglobin expression profile. Sequencing results validated by reverse-transcription quantitative PCR (RT-qPCR) of selected miRNAs indicate shared differentiation signatures in primary and immortalized cells, characterized by reduced overall miRNA expression and reciprocal expression increases for individual lineage-specific miRNAs in late-stage erythropoiesis. Despite the high similarity of same-stage hCD34+ and HUDEP-2 cells, differential expression of several miRNAs highlighted informative discrepancies between both cell types. Moreover, a comparison between HUDEP-2 and HUDEP-1 cells displayed changes in miRNAs, transcription factors (TFs), target genes, and pathways associated with globin switching. In resulting TF-miRNA co-regulatory networks, major therapeutically relevant regulators of globin expression were targeted by many co-expressed miRNAs, outlining intricate combinatorial miRNA regulation of globin expression in erythroid cells. View Full-Text
Keywords: microRNA; non-coding DNA; small RNA sequencing; erythropoiesis; CD34+; hematopoietic stem cell; gene regulatory network; long non-coding RNA; competing endogenous RNA; enrichment analysis; developmental regulation microRNA; non-coding DNA; small RNA sequencing; erythropoiesis; CD34+; hematopoietic stem cell; gene regulatory network; long non-coding RNA; competing endogenous RNA; enrichment analysis; developmental regulation
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MDPI and ACS Style

Papasavva, P.L.; Papaioannou, N.Y.; Patsali, P.; Kurita, R.; Nakamura, Y.; Sitarou, M.; Christou, S.; Kleanthous, M.; Lederer, C.W. Distinct miRNA Signatures and Networks Discern Fetal from Adult Erythroid Differentiation and Primary from Immortalized Erythroid Cells. Int. J. Mol. Sci. 2021, 22, 3626. https://doi.org/10.3390/ijms22073626

AMA Style

Papasavva PL, Papaioannou NY, Patsali P, Kurita R, Nakamura Y, Sitarou M, Christou S, Kleanthous M, Lederer CW. Distinct miRNA Signatures and Networks Discern Fetal from Adult Erythroid Differentiation and Primary from Immortalized Erythroid Cells. International Journal of Molecular Sciences. 2021; 22(7):3626. https://doi.org/10.3390/ijms22073626

Chicago/Turabian Style

Papasavva, Panayiota L., Nikoletta Y. Papaioannou, Petros Patsali, Ryo Kurita, Yukio Nakamura, Maria Sitarou, Soteroulla Christou, Marina Kleanthous, and Carsten W. Lederer. 2021. "Distinct miRNA Signatures and Networks Discern Fetal from Adult Erythroid Differentiation and Primary from Immortalized Erythroid Cells" International Journal of Molecular Sciences 22, no. 7: 3626. https://doi.org/10.3390/ijms22073626

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