MicroRNAs Key Regulators of Blood Cell Development

HSCs reside in the bone marrow and are self-renewing. When HSCs proliferate, at least some of their daughter cells remain as HSCs, so the pool of stem cells does not become depleted. The other daughters of HSCs (myeloid and lymphoid progenitor cells) are able to commit to any of the alternative differentiation pathways that lead to the production of one or more specific types of blood cells, but cannot self-renew. The mechanism that determines the fate of HSCs has not been well understood.

Since microRNAs (miRNAs) are now recognized as master controllers of cellular metabolism, investigators at the University of Toronto (Canada) examined their possible role in the regulation of HSC proliferation.

They reported in the November 8, 2012, online edition of the journal Cell Stem Cell that a particular miRNA, miR-126, was a novel regulator of the processes governing HSC quiescence or growth and proliferation. Reduction in miR-126 levels induced an expansion of long-term HSCs without exhaustion, while constitutive miR-126 expression promoted HSC quiescence and the proliferation of myeloid and lymphoid progenitor cells.

“For the first time in human blood stem cells, we have established that a new class of noncoding RNA called miRNA represents a new tactic for manipulating these cells, which opens the door to expanding them for therapeutic uses,” said contributing author Dr. John Dick, professor of molecular genetics at the University of Toronto. “We have shown that if you remove the miRNA you can expand the stem cells while keeping their identity intact. That is the key to long-term stem cell expansion for use with patients.”

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