Mitochondrial state determines functionally divergent stem cell population in planaria

Stem Cell Reports. 2021 May 11;16(5):1302-1316. doi: 10.1016/j.stemcr.2021.03.022. Epub 2021 Apr 15.


Mitochondrial state changes were shown to be critical for stem cell function. However, variation in the mitochondrial content in stem cells and the implication, if any, on differentiation is poorly understood. Here, using cellular and molecular studies, we show that the planarian pluripotent stem cells (PSCs) have low mitochondrial mass compared with their progenitors. Transplantation experiments provided functional validation that neoblasts with low mitochondrial mass are the true PSCs. Further, the mitochondrial mass correlated with OxPhos and inhibiting the transition to OxPhos dependent metabolism in cultured cells resulted in higher PSCs. In summary, we show that low mitochondrial mass is a hallmark of PSCs in planaria and provide a mechanism to isolate live, functionally active, PSCs from different cell cycle stages (G0/G1 and S, G2/M). Our study demonstrates that the change in mitochondrial metabolism, a feature of PSCs is conserved in planaria and highlights its role in organismal regeneration.

Keywords: FACS; differentiation; mitochondria; neoblasts; planaria; pluripotency; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Membrane Potential, Mitochondrial
  • Mitochondria / metabolism*
  • Planarians / cytology*
  • Planarians / genetics
  • Planarians / metabolism*
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism
  • RNA, Small Interfering / metabolism
  • RNA-Seq
  • Staining and Labeling
  • Stem Cell Transplantation
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transcriptome / genetics


  • RNA, Small Interfering