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The long non-coding RNA (lncRNA)  M aternally  E xpressed  G ene 3 ( Meg3 ) is encoded within the imprinted  Dlk1-Meg3  gene locus and is only maternally expressed.  Meg3  has been shown to play an important role in the regulation of cellular proliferation and functions as a tumor suppressor in numerous tissues.  Meg3  is highly expressed in mouse adult hematopoietic stem cells (HSCs) and strongly down-regulated in early progenitors. To address its functional role in HSCs, we used MxCre to conditionally delete  Meg3  in the adult bone marrow of Meg3 mat-flox/pat-wt  mice. We performed extensive  in vitro  and  in vivo  analyses of mice carrying a  Meg3  deficient blood system, but neither observed impaired hematopoiesis during homeostatic conditions nor upon serial transplantation. Furthermore, we analyzed VavCre Meg3 mat-flox/pat-wt  mice, in which  Meg3  was deleted in the embryonic hematopoietic system and unexpectedly this did neither generate any hematopoietic defects. In response to interferon-mediated stimulation,  Meg3  deficient adult HSCs responded highly similar compared to controls. Taken together, we report the finding, that the highly expressed imprinted lncRNA  Meg3  is dispensable for the function of HSCs during homeostasis and in response to stress mediators as well as for serial reconstitution of the blood system  in vivo .

The long non-coding RNA Meg3 is dispensable for hematopoietic stem cells