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New miRNA Inhibition Technology Helps to Explore the Developing Dental Stem Cell Niche

Review of The miR‐200 family is required for ectodermal organ development through the regulation of the epithelial stem cell niche from STEM CELLS by Stuart P. Atkinson

Previous research from the laboratory of Brad A. Amendt (University of Iowa, Iowa City, IA, USA) established the relative importance of the miR‐200 family (formed of five mature micro (mi)RNAs from two clusters) to the differentiation of the mouse dental epithelial stem cells (DESCs) [1], which contribute to the formation of the lower incisor [2, 3]. The team also developed a “plasmid-based miR inhibitor system” (PMIS) [4] that allows a single inhibitor to functionally inhibit miRNAs with identical seed sequences and establish stable cell/mouse lines for functional in vitro and in vivo studies.

In their recent STEM CELLS article [5], Sweat et al. employed the PMIS system to evaluate the loss of the miR‐200a/141 (PMIS‐miR‐200a) and miR‐200b/c/429 (PMIS‐miR‐200c) functional groups in mouse embryos and now report that the miR‐200 family compartmentalizes the DESC niche by regulating progenitor cell differentiation during development.

Here are the headlines from this exciting new study that discovered how inhibiting the miR‐200 family in developing mouse embryos prompted the expansion of the DESC niche and the inhibition of cell differentiation:

  • The inhibition of individual members of the miR‐200 cluster resulted in differential developmental and cell morphology defects
  • miR‐200 inhibition increased the expression of DESC markers, expanded the DESC niche, and decreased progenitor cell differentiation
    • These findings suggest the normal function of miR-200 in compartmentalizing and maintaining the DESC niche, with Sox2 expression a crucial controlling factor
    • miR‐200 inhibition also decreased lower incisor size due to increased autophagy/cell death and reduced the expression of genes associated with enamel formation
  • RNA‐sequencing identified miR‐200 regulatory pathways involved in cell differentiation, compartmentalization of the stem cell niche, and cell cycle progression

Overall, this exciting new study provides evidence for the utility of the plasmid-based miR inhibitor system and demonstrates how the expression of the miR-200 family regulates the fate of cells of the developing DESC niche.

For more on miRNAs, dental epithelial stem cells, and the control of gene expression during development, stay tuned to the Stem Cells Portal!

References

  1. Cao H, Wang J, Li X, et al., MicroRNAs Play a Critical Role in Tooth Development. Journal of Dental Research 2010;89:779-784.
  2. Hsu Y-C, Li L, and Fuchs E, Transit-Amplifying Cells Orchestrate Stem Cell Activity and Tissue Regeneration. Cell 2014;157:935-949.
  3. Wang X-P, Suomalainen M, Felszeghy S, et al., An Integrated Gene Regulatory Network Controls Stem Cell Proliferation in Teeth. PLOS Biology 2007;5:e159.
  4. Cao H, Yu W, Li X, et al., A new plasmid-based microRNA inhibitor system that inhibits microRNA families in transgenic mice and cells: a potential new therapeutic reagent. Gene Therapy 2016;23:527-542.
  5. Sweat M, Sweat Y, Yu W, et al., The miR-200 family is required for ectodermal organ development through the regulation of the epithelial stem cell niche. STEM CELLS 2021;39:761-775.