TY - JOUR
T1 - Enteroendocrine and tuft cells support Lgr5 stem cells on Paneth cell depletion
AU - Van Es, Johan H.
AU - Wiebrands, Kay
AU - López-Iglesias, Carmen
AU - Van De Wetering, Marc
AU - Zeinstra, Laura
AU - Van Den Born, Maaike
AU - Korving, Jeroen
AU - Sasaki, Nobuo
AU - Peters, Peter J.
AU - Van Oudenaarden, Alexander
AU - Clevers, Hans
N1 - Funding Information:
We thank Stefan van der Elst for assisting with the FACS sorting experiments and Harry Begthel for performing some of the histological stainings.
Publisher Copyright:
© 2019 National Academy of Sciences. All rights reserved.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2019/12/26
Y1 - 2019/12/26
N2 - Cycling intestinal Lgr5+ stem cells are intermingled with their terminally differentiated Paneth cell daughters at crypt bottoms. Paneth cells providemultiple secreted (e.g.,Wnt, EGF) aswell as surfacebound (Notch ligand) niche signals. Here we show that ablation of Paneth cells in mice, using a diphtheria toxin receptor gene inserted into the P-lysozyme locus, does not affect the maintenance of Lgr5+ stem cells. Flow cytometry, single-cell sequencing, and histological analysis showed that the ablated Paneth cells are replaced by enteroendocrine and tuft cells. As these cells physically occupy Paneth cell positions between Lgr5 stem cells, they serve as an alternative source of Notch signals, which are essential for Lgr5+ stem cell maintenance. Our combined in vivo results underscore the adaptive flexibility of the intestine in maintaining normal tissue homeostasis.
AB - Cycling intestinal Lgr5+ stem cells are intermingled with their terminally differentiated Paneth cell daughters at crypt bottoms. Paneth cells providemultiple secreted (e.g.,Wnt, EGF) aswell as surfacebound (Notch ligand) niche signals. Here we show that ablation of Paneth cells in mice, using a diphtheria toxin receptor gene inserted into the P-lysozyme locus, does not affect the maintenance of Lgr5+ stem cells. Flow cytometry, single-cell sequencing, and histological analysis showed that the ablated Paneth cells are replaced by enteroendocrine and tuft cells. As these cells physically occupy Paneth cell positions between Lgr5 stem cells, they serve as an alternative source of Notch signals, which are essential for Lgr5+ stem cell maintenance. Our combined in vivo results underscore the adaptive flexibility of the intestine in maintaining normal tissue homeostasis.
KW - Intestine
KW - Notch
KW - Paneth cells
KW - Stem cells
UR - http://www.scopus.com/inward/record.url?scp=85077342908&partnerID=8YFLogxK
U2 - 10.1073/pnas.1801888117
DO - 10.1073/pnas.1801888117
M3 - Article
C2 - 31843916
AN - SCOPUS:85077342908
SN - 0027-8424
VL - 116
SP - 26599
EP - 26605
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 52
ER -