Coupling organelle inheritance with mitosis to balance growth and differentiation.
Balancing growth and differentiation is essential to tissue morphogenesis and homeostasis. How imbalances arise in disease states is poorly understood. To address this issue, we identified transcripts differentially expressed in mouse basal epidermal progenitors versus their differentiating progeny and those altered in cancers. We used an in vivo RNA interference screen to unveil candidates that altered the equilibrium between the basal proliferative layer and suprabasal differentiating layers forming the skin barrier. We found that epidermal progenitors deficient in the peroxisome-associated protein Pex11b failed to segregate peroxisomes properly and entered a mitotic delay that perturbed polarized divisions and skewed daughter fates. Together, our findings unveil a role for organelle inheritance in mitosis, spindle alignment, and the choice of daughter progenitors to differentiate or remain stem-like.
Howard Hughes Medical Institute, Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA.
Amma
A
Asare
Howard Hughes Medical Institute, Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA.
John
J
Levorse
Howard Hughes Medical Institute, Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA. fuchslb@rockefeller.edu.
Elaine
E
Fuchs
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology*; D015870:Gene Expression; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*; D020675:Peroxisomes / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference; D008941:Spindle Apparatus / Q000502:physiology; D013234:Stem Cells / Q000166:cytology*; D059467:Transcriptome
D008565:Membrane Proteins; C490452:Pex11b protein, mouse