Comprehensive Analysis of microRNAs in Human Adult Erythropoiesis

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs, which play an important role in various cellular and developmental processes. The study of miRNAs in erythropoiesis is crucial to uncover the cellular pathways that are modulated during the different stages of erythroid differentiation. Using erythroid cells derived from human CD34+ hematopoietic stem and progenitor cells (HSPCs)and small RNA sequencing, our study unravels the various miRNAs involved in critical cellular pathways in erythroid maturation. We analyzed the occupancy of erythroid transcription factors and chromatin accessibility in the promoter and enhancer regions of the differentially expressed miRNAs to integrate miRNAs in the transcriptional circuitry of erythropoiesis. Analysis of the targets of the differentially expressed miRNAs revealed novel pathways in erythroid differentiation. Finally, we described the application of Clustered regularly interspaced short palindromic repeats-Cas9 (CRISPR-Cas9) based editing of miRNAs to study their function in human erythropoiesis.

“Transcriptional repression of lncRNA and miRNA subsets mediated by LRF during erythropoiesis”

“…Two miR clusters including miR182-5p and miR-125a-5p, miR99b-5p and let-7e-5p respectively, simultaneously with single miRs, miR-486-5p and miR3529-3p, were significantly upregulated upon erythropoiesis induction in both UT+hemin/EPO and LRF-OE+hemin/EPO, indicating the cell commitment to the erythroid lineage. These results are in consistency with other reported data [48]. MiR-126-5p was a unique case with repressed expression during erythropoiesis induction of UT with hemin/EPO treatment (Supplementary table 3).…”

Selective Loading and Variations in the miRNA Profile of Extracellular Vesicles from Endothelial-like Cells Cultivated under Normoxia and Hypoxia

“…Interestingly, there are few descriptions of miR-12136 in literature. Recently, it was identified during erythropoiesis [ 62 ], in adipose-derived stem cells from old or diabetic patients [ 63 ], in the secretome of menstrual blood-derived MSC [ 64 ]. miR-12136 was also found to be downregulated in EVs from adipose-derived MSC from patients with metabolic syndrome [ 65 ] and was enriched in human vascular smooth muscle cells during replicative senescence [ 66 ].…”

Erythrocytes as Messengers for Information and Energy Exchange between Cells

“…FoxO3 positively regulates antioxidant enzymes like catalase and glutathione peroxidase. CRISPR-Cas9-mediated mutagenesis of miR451 confirmed that miR451 is necessary for erythroid differentiation and expression of transferrin receptor 1, also known as CD71 [163]. The miR144 family is expressed together with miR451 and was similarly found to be necessary for erythroid differentiation and CD71 expression [163].…”

“…Once in the cytoplasm, the miRNA is further processed by Dicer and bound to Argonaute2 forming the RNA-induced silencing (RISC) complex. Some of the miRNAs of the erythrocyte like miR-451, miR-144, and miR-486 are involved in erythropoiesis [163]. MiR-451 is also associated with malaria, and miR-144 is correlated with hypoxia at high altitudes [159].…”

“…CRISPR-Cas9-mediated mutagenesis of miR451 confirmed that miR451 is necessary for erythroid differentiation and expression of transferrin receptor 1, also known as CD71 [163]. The miR144 family is expressed together with miR451 and was similarly found to be necessary for erythroid differentiation and CD71 expression [163]. Plasmodium-infected erythrocytes produce microvesicles containing miR451, miR16, and let-7, among others [167][168][169].…”