The Mi-2-like Smed-CHD4 gene is required for stem cell differentiation in the planarian Schmidtea mediterranea.
Freshwater planarians are able to regenerate any missing part of their body and have extensive tissue turnover because of the action of dividing cells called neoblasts. Neoblasts provide an excellent system for in vivo study of adult stem cell biology. We identified the Smed-CHD4 gene, which is predicted to encode a chromatin-remodeling protein similar to CHD4/Mi-2 proteins, as required for planarian regeneration and tissue homeostasis. Following inhibition of Smed-CHD4 with RNA interference (RNAi), neoblast numbers were initially normal, despite an inability of the animals to regenerate. However, the proliferative response of neoblasts to amputation or growth stimulation in Smed-CHD4(RNAi) animals was diminished. Smed-CHD4(RNAi) animals displayed a dramatic reduction in the numbers of certain neoblast progeny cells. Smed-CHD4 was required for the formation of these neoblast progeny cells. Together, these results indicate that Smed-CHD4 is required for neoblasts to produce progeny cells committed to differentiation in order to control tissue turnover and regeneration and suggest a crucial role for CHD4 proteins in stem cell differentiation.
Howard Hughes Medical Institute, Whitehead Institute, 9 Cambridge Center, Cambridge, MA 02142, USA.
M Lucila
ML
Scimone
Joshua
J
Meisel
Peter W
PW
Reddien
D000818:Animals; D001324:Autoantigens / Q000235:genetics*; D001973:Bromodeoxyuridine; D002454:Cell Differentiation; D002455:Cell Division; D004265:DNA Helicases / Q000235:genetics; D005434:Flow Cytometry; D010932:Planarians / Q000166:cytology / Q000235:genetics* / Q000502:physiology; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics; D013234:Stem Cells / Q000166:cytology*
D001324:Autoantigens; D012313:RNA; D004265:DNA Helicases; D001973:Bromodeoxyuridine