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MicroRNAs: key regulators of stem cells

Key Points

  • Embryonic and adult tissue stem cells are characterized by their ability to self-renew and to differentiate into daughter cells, which in adult tissue stem cells is often achieved by asymmetric divisions.

  • MicroRNAs (miRNAs) are 20–25-nucleotide (nt)-long non-coding RNAs that bind to the 3′ untranslated region of target mRNAs via imperfect match to repress their translation and stability.

  • miRNAs fine-tune self-renewal and differentiation pathways of stem cells by regulating the intracellular levels of the key protein factors that are involved in these processes. It is now clear that a number of miRNAs that are involved in stem cell processes are co-expressed as clusters and can function as 'master regulators' of stem cell processes.

  • miRNAs and the transcriptional machinery form an integral network that regulates stem cell processes.

  • In addition to miRNA, there are two other types of small RNAs: endogenous small interfering RNAs (endo-siRNAs) and Piwi-interacting RNAs (piRNAs). Their presence and function in stem cells is not known.

  • The recent advent of next generation sequencing technologies has increased our ability to identify new miRNAs and other small RNAs in various tissues.


The hallmark of a stem cell is its ability to self-renew and to produce numerous differentiated cells. This unique property is controlled by dynamic interplays between extrinsic signalling, epigenetic, transcriptional and post-transcriptional regulations. Recent research indicates that microRNAs (miRNAs) have an important role in regulating stem cell self-renewal and differentiation by repressing the translation of selected mRNAs in stem cells and differentiating daughter cells. Such a role has been shown in embryonic stem cells, germline stem cells and various somatic tissue stem cells. These findings reveal a new dimension of gene regulation in controlling stem cell fate and behaviour.

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Figure 1: RNA regulation of embryonic stem cells.
Figure 2: RNA regulation of haematopoietic stem cells.


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We thank members of the Lin laboratory for their valuable comments on the manuscript. We apologize to those whose works are not cited here owing to space limitations. The stem cell work done in the Lin laboratory is supported by National Institutes of Health Grants HD33760, HD37760S1 and HD42042, the Connecticut Stem Cell Research Fund, the G. Harold and Leila Mathers Foundation and the Stem Cell Research Foundation.

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Correspondence to Haifan Lin.

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An early stage of embryonic development at which cells begin to commit to two developmental lineages: the inner cell mass, which gives rise to the fetus, and the trophoblast, which gives rise to fetal support tissues, such as the placenta and the umbilical cord.


The natural anatomical microenvironment that supports stem cell behaviour.


A ribonucleoprotein (RNP) complex that is involved in splicing of nuclear pre-mRNA. It is composed of five small nuclear (sn) RNPs and more than 50 non-snRNPs, which recognize and assemble on exon–intron boundaries to catalyse intron processing of the pre-mRNA.


An Argonaute or Piwi protein family member in Drosophila melanogaster that is required for germline stem cell self-renewal and also binds to 25 nucleotide small RNAs. Piwi is the founding member that was used to define the protein family.


A mobile genetic element that can relocate within the genome of its host. An autonomous transposon encodes a transposase protein that catalyses its excision and reintegration in the genome, and can therefore direct its own transposition.

Gap junction

An intercellular connection that directly connects cytoplasm of two cells so that exchange of molecules and ions can occur freely.


An undifferentiated cell in annelids that proliferates to produce differentiated cells at the sites of repair.

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Gangaraju, V., Lin, H. MicroRNAs: key regulators of stem cells. Nat Rev Mol Cell Biol 10, 116–125 (2009).

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