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Stem Cell Fate and the Peroxisome: An Unexpected Link

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Review of “Coupling organelle inheritance with mitosis to balance growth and differentiation” from Science by Stuart P. Atkinson

Tissue development and homeostasis rely on a balance between resident stem cell self-renewal and differentiation to somatic cell types. In the case of the epidermis, basal progenitors control the presence of a terminally differentiated polarized cell layer that acts as an important two-way barrier; microbes out, body fluids in! However, imbalances in self-renewal or differentiation can lead to hyperproliferative disorders and cancers or aging and wound healing defects, respectively, but concrete molecular links remain undescribed. 

Now, a new study from the laboratory of Elaine Fuchs (Rockefeller University, New York, USA) aimed to discover the molecular mechanisms that control stem cell fate and uncovered an unexpected link! Their new Science study suggests that mitotic progression, epidermal stem cell fate decisions, and epidermal barrier formation all require the proper localization of organelles known as peroxisomes [1].

The author’s initial studies employed RNA sequencing and RNA interference screens to reveal genes important to the early commitment of epidermal progenitors to terminally differentiated cells and those genes mutated in human epithelial cancers. Unexpectedly, this analysis implicated the peroxisomal gene PEX11b, although the authors found no link between epidermal stem cell fate and the fatty acid and energy metabolism roles of the peroxisome organelle. Instead, the loss of PEX11b in epidermal stem cells led to the loss of normal peroxisome partitioning to epidermal daughter cells during mitosis. This disruption to normal organelle inheritance elicited a checkpoint-like state, disrupted epidermal terminal differentiation, and altered cell polarity leading to a loss of epidermal barrier function.

While this study uncovered an “unexpected link” between stem cell fate and the peroxisome, previous studies had already indicated a requirement for proper organelle organization in adult stem cells [2]. Therefore, organized organelle inheritance may represent an important principle for tissue development and homeostasis and further studies may provide new insights into cancer development and aid the construction of new cancer therapeutics in various tissues.

What organelle will be next? Be sure to check out the Stem Cells Portal to hear all the new updates on this fascinating emerging area of study. 

References

  1. Asare A, Levorse J, and Fuchs E. Coupling organelle inheritance with mitosis to balance growth and differentiation. Science 2017;355:
  2. Katajisto P, Dohla J, Chaffer CL, et al. Stem cells. Asymmetric apportioning of aged mitochondria between daughter cells is required for stemness. Science 2015;348:340-343.