The mirn23a and mirn23b microrna clusters are necessary for proper hematopoietic progenitor cell production and differentiation

Experimental Hematology
Jeffrey L KurkewichRichard Dahl

Abstract

Mice deficient for microRNA (miRNA) cluster mirn23a exhibit increased B lymphopoiesis at the expense of myelopoiesis, whereas hematopoietic stem and progenitor cell (HSPC) populations are unchanged. Mammals possess a paralogous mirn23b gene that can give rise to three mature miRNAs (miR-23b, miR-24-1, and miR-27b) that have identical seed/mRNA-targeting sequences to their mirn23a counterparts. To assess whether compound deletion of mirn23a and mirn23b exacerbates the hematopoietic phenotype observed in mirn23a-/- mice, we generated a compound mirn23a-/-mirn23bfl/fl:Mx1-Cre conditional knockout mouse and assayed hematopoietic development after excision of mirn23b. Loss of both genes in adult bone marrow further skewed HSPC differentiation toward B cells at the expense of myeloid cells, demonstrating a dosage-dependent effect on regulating cell differentiation. Strikingly, double-knockout (DKO) mice had decreased bone marrow cellularity with significantly decreased hematopoietic stem cell and HSPC populations, a phenotype not observed in mice deficient for mirn23a alone. Competitive transplantation assays showed decreased contribution of mirn23a-/-mirn23b-/- HSPCs to hematopoietic lineages at 6 and 12 weeks after transplantation....Continue Reading

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Citations

Oct 28, 2020·PLoS Pathogens·Mike KhanJudith A Smith
Jun 9, 2020·Mechanisms of Ageing and Development·Daniëlle Gaby Luinenburg, Gerald de Haan
Jan 13, 2021·International Journal of Molecular Sciences·Yong-Hui JiangShi-Gang Zhao
Jan 2, 2021·Non-coding RNA Research·Soudeh Ghafouri-FardMohammad Taheri
Sep 18, 2021·Wiley Interdisciplinary Reviews. RNA·Laura Crisafulli, Francesca Ficara

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