TY - JOUR
T1 - Distinct ATOH1 and Neurog3 requirements define tuft cells as a new secretory cell type in the intestinal epithelium
AU - Gerbe, François
AU - Van Es, Johan H.
AU - Makrini, Leila
AU - Brulin, Bénédicte
AU - Mellitzer, Georg
AU - Robine, Sylvie
AU - Romagnolo, Béatrice
AU - Shroyer, Noah F.
AU - Bourgaux, Jean François
AU - Pignodel, Christine
AU - Clevers, Hans
AU - Jay, Philippe
PY - 2011/3/7
Y1 - 2011/3/7
N2 - The unique morphology of tuft cells was first revealed by electron microscopy analyses in several endoderm-derived epithelia. Here, we explore the relationship of these cells with the other cell types of the intestinal epithelium and describe the first marker signature allowing their unambiguous identification. We demonstrate that although mature tuft cells express DCLK1, a putative marker of quiescent stem cells, they are post-mitotic, short lived, derive from Lgr5-expressing epithelial stem cells, and are found in mouse and human tumors. We show that whereas the ATOH1/MATH1 transcription factor is essential for their differentiation, Neurog3, SOX9, GFI1, and SPDEF are dispensable, which distinguishes these cells from enteroendocrine, Paneth, and goblet cells, and raises from three to four the number of secretory cell types in the intestinal epithelium. Moreover, we show that tuft cells are the main source of endogenous intestinal opioids and are the only epithelial cells that express cyclooxygenase enzymes, suggesting important roles for these cells in the intestinal epithelium physiopathology.
AB - The unique morphology of tuft cells was first revealed by electron microscopy analyses in several endoderm-derived epithelia. Here, we explore the relationship of these cells with the other cell types of the intestinal epithelium and describe the first marker signature allowing their unambiguous identification. We demonstrate that although mature tuft cells express DCLK1, a putative marker of quiescent stem cells, they are post-mitotic, short lived, derive from Lgr5-expressing epithelial stem cells, and are found in mouse and human tumors. We show that whereas the ATOH1/MATH1 transcription factor is essential for their differentiation, Neurog3, SOX9, GFI1, and SPDEF are dispensable, which distinguishes these cells from enteroendocrine, Paneth, and goblet cells, and raises from three to four the number of secretory cell types in the intestinal epithelium. Moreover, we show that tuft cells are the main source of endogenous intestinal opioids and are the only epithelial cells that express cyclooxygenase enzymes, suggesting important roles for these cells in the intestinal epithelium physiopathology.
UR - http://www.scopus.com/inward/record.url?scp=79952418471&partnerID=8YFLogxK
U2 - 10.1083/jcb.201010127
DO - 10.1083/jcb.201010127
M3 - Article
C2 - 21383077
AN - SCOPUS:79952418471
SN - 0021-9525
VL - 192
SP - 767
EP - 780
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 5
ER -