MicroRNAs Modulate Hematopoietic Lineage Differentiation

TLDR

MicroRNAs are abundant ~22‑nt regulatory RNAs in plants and animals that modulate gene expression during development. The study identifies three hematopoietic‑specific miRNAs and demonstrates their dynamic regulation during early hematopoiesis and lineage commitment. Ectopic expression of miR‑181 in hematopoietic stem/progenitor cells increases B‑lineage differentiation, indicating that microRNAs are integral components of the molecular circuitry controlling mouse hematopoiesis and likely other vertebrate developmental processes.

Abstract

MicroRNAs (miRNAs) are an abundant class of approximately 22-nucleotide regulatory RNAs found in plants and animals. Some miRNAs of plants, Caenorhabditis elegans, and Drosophila play important gene-regulatory roles during development by pairing to target mRNAs to specify posttranscriptional repression of these messages. We identify three miRNAs that are specifically expressed in hematopoietic cells and show that their expression is dynamically regulated during early hematopoiesis and lineage commitment. One of these miRNAs, miR-181, was preferentially expressed in the B-lymphoid cells of mouse bone marrow, and its ectopic expression in hematopoietic stem/progenitor cells led to an increased fraction of B-lineage cells in both tissue-culture differentiation assays and adult mice. Our results indicate that microRNAs are components of the molecular circuitry that controls mouse hematopoiesis and suggest that other microRNAs have similar regulatory roles during other facets of vertebrate development.