MicroRNA Expression Profiles in Umbilical Cord Blood Cell Lineages

Abstract

MicroRNAs (miRNAs), important regulators of cellular processes, show specific expression signatures in different blood cell lineages and stages of hematopoietic stem cell (HSC) differentiation, indicating their role in the control of hematopoiesis. Because neonatal blood displays various features of immaturity, we might expect differential miRNA regulation. Herein, we determined miRNA expression profiles of umbilical cord blood (UCB) cell lineages and compared them to those of bone marrow (BM) and peripheral blood (PB) cell counterparts. Further, we determined mRNA expression profiles using whole-genome microarrays. An approach combining bioinformatic prediction of miRNA targets with mRNA expression profiling was used to search for putative targets of miRNAs with potential functions in UCB. We pointed out several differentially expressed miRNAs and associated their expression with the target transcript levels. miR-148a expression was suppressed in HSCs and its level inversely correlated with the previously verified target, DNA methyltransferase 3B, suggesting dependence of de novo DNA methylation in HSCs on miR-148a. Prolonged cell survival of UCB HSCs may be associated with low expression of miR-143 and miR-145 and up-regulation of their downstream targets (high expression of c-MYC and miR-17-92 and following repression of TGFBR2). In HSCs, we monitored significant up-regulation of eight miRNAs, which were previously verified as regulators of HOX genes. Further, miR-146b may be associated with immaturity of neonatal immune system because it is strongly up-regulated in UCB granulocytes and T lymphocytes compared to PB cell counterparts. Comparative analysis revealed 13 miRNAs significantly altered between UCB and BM CD34(+) cells. In UCB CD34(+) cells, we monitored up-regulation of miR-520h, promoting differentiation of HSCs into progenitor cells, and reduction of miR-214, whose expression might support HSC survival. In conclusion, UCB cells show specific miRNA expression patterns, indicating different regulation in these cells.

MicroRNAs Contribute to Induced Pluripotent Stem Cell Somatic Donor Memory

“…In this regard, miRNAs have a crucial role in the induction of differentiation toward myeloid and lymphoid lineages or in the maintenance of self-renewal (41). Several studies have reported a group of miRNAs up-regulated in HPCs isolated from different sources, including those observed in our study (27,31,46,47). However, although miR-155 was also identified in previous studies, herein we validated for the first time its mRNA targets in the context of maintenance of the HPC phenotype.…”

“…Interestingly, the miRNAs whose expression levels increased along time points were mostly described as miRNAs associated with embryonic pluripotency states (miR-302-367 cluster; miR-183) (25,26). Conversely, the miRNAs displaying DD and ED expression trends in CBiPSCs were previously associated with differentiation of ESCs or hematopoiesis (Let-7 family, miR-125b, miR-155, and miR99a) (27)(28)(29)(30) or described to be up-regulated in neoplastic diseases (miR-3162 and miR-3921) (31)(32)(33)(34)(35) (Fig. 3A).…”

Deregulation of microRNAs in myelodysplastic syndrome

“…Differences in miRNA expression between umbilical cord and adult BM CD34 þ cells were also investigated. 24 Thirteen miRNAs were differentially expressed between umbilical cord and BM CD34 þ cells: miR-548d, miR-203, miR-1, miR-34a, miR-545, let-7b, miR-429, miR-214, miR-195, miR-520h, miR-518a, miR-519d and miR-517c.…”

Reviewing and Updating the Major Molecular Markers for Stem Cells

“…Merkerova et al [232] detected differences in the miRNAs expressed by HSCs obtained from bone marrow and umbilical cord blood. Bone marrow-derived CD34…”