PMID- 21113151
OWN - NLM
STAT- MEDLINE
DCOM- 20110217
LR  - 20240104
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 469
IP  - 7330
DP  - 2011 Jan 20
TI  - Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts.
PG  - 415-8
LID - 10.1038/nature09637 [doi]
AB  - Homeostasis of self-renewing small intestinal crypts results from neutral 
      competition between Lgr5 stem cells, which are small cycling cells located at 
      crypt bottoms. Lgr5 stem cells are interspersed between terminally differentiated 
      Paneth cells that are known to produce bactericidal products such as lysozyme and 
      cryptdins/defensins. Single Lgr5-expressing stem cells can be cultured to form 
      long-lived, self-organizing crypt-villus organoids in the absence of 
      non-epithelial niche cells. Here we find a close physical association of Lgr5 
      stem cells with Paneth cells in mice, both in vivo and in vitro. CD24(+) Paneth 
      cells express EGF, TGF-alpha, Wnt3 and the Notch ligand Dll4, all essential signals 
      for stem-cell maintenance in culture. Co-culturing of sorted stem cells with 
      Paneth cells markedly improves organoid formation. This Paneth cell requirement 
      can be substituted by a pulse of exogenous Wnt. Genetic removal of Paneth cells 
      in vivo results in the concomitant loss of Lgr5 stem cells. In colon crypts, 
      CD24(+) cells residing between Lgr5 stem cells may represent the Paneth cell 
      equivalents. We conclude that Lgr5 stem cells compete for essential niche signals 
      provided by a specialized daughter cell, the Paneth cell.
FAU - Sato, Toshiro
AU  - Sato T
AD  - Hubrecht Institute, KNAW and University Medical Center Utrecht, Uppsalalaan 8, 
      3584CT Utrecht, the Netherlands.
FAU - van Es, Johan H
AU  - van Es JH
FAU - Snippert, Hugo J
AU  - Snippert HJ
FAU - Stange, Daniel E
AU  - Stange DE
FAU - Vries, Robert G
AU  - Vries RG
FAU - van den Born, Maaike
AU  - van den Born M
FAU - Barker, Nick
AU  - Barker N
FAU - Shroyer, Noah F
AU  - Shroyer NF
FAU - van de Wetering, Marc
AU  - van de Wetering M
FAU - Clevers, Hans
AU  - Clevers H
LA  - eng
SI  - GEO/GSE25109
GR  - R01 CA142826/CA/NCI NIH HHS/United States
GR  - R01 CA142826-01/CA/NCI NIH HHS/United States
GR  - R03 DK084167/DK/NIDDK NIH HHS/United States
GR  - R03 DK084167-01/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20101128
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (CD24 Antigen)
RN  - 0 (Lgr5 protein, mouse)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (WNT3 protein, human)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt3 Protein)
RN  - 0 (Wnt3 protein, mouse)
SB  - IM
MH  - Animals
MH  - CD24 Antigen/metabolism
MH  - Cell Count
MH  - Cell Proliferation
MH  - Coculture Techniques
MH  - Humans
MH  - Intestines/*cytology
MH  - Mice
MH  - Multipotent Stem Cells/*cytology/*metabolism
MH  - Paneth Cells/*cytology/metabolism
MH  - Receptors, G-Protein-Coupled/*metabolism
MH  - Stem Cell Niche/*cytology/metabolism
MH  - Wnt Proteins/metabolism
MH  - Wnt3 Protein
PMC - PMC3547360
MID - NIHMS301786
COIS- Declaration of competing financial interests H.C. is an inventor on several 
      patents involving the culture system in this paper, as is T.S.
EDAT- 2010/11/30 06:00
MHDA- 2011/02/18 06:00
PMCR- 2013/01/17
CRDT- 2010/11/30 06:00
PHST- 2010/03/26 00:00 [received]
PHST- 2010/11/04 00:00 [accepted]
PHST- 2010/11/30 06:00 [entrez]
PHST- 2010/11/30 06:00 [pubmed]
PHST- 2011/02/18 06:00 [medline]
PHST- 2013/01/17 00:00 [pmc-release]
AID - nature09637 [pii]
AID - 10.1038/nature09637 [doi]
PST - ppublish
SO  - Nature. 2011 Jan 20;469(7330):415-8. doi: 10.1038/nature09637. Epub 2010 Nov 28.