Cdx2
Proximodistal organization
Gata4Represses Ileal gene program
Differentiated cellcompartment
Transient-amplifyingcompartment
Stem cell niche
Duodenum Jejunum Ileum Prox. colon Dist. colon
Caecum
Represses stomachgene program
M cell Enterocyte Goblet Endocrine
NeuroDElf3Cdx2+Hnf4
Elf3Spdef
Pax4/6Nkx2.2
RankL
Notch Dll1/4Absorptiveprogenitor
Secretory progenitor
Sox9Spdef
Math1 +WNT
Dama
ge
Damage
Paneth cellISCs(Lgr5+)
Spi-BNgn3?
?
Tuft
LRC(Lgr5+)
Hes1 Math1
Cell hierarchy and lineage specification
TIME
Restricted nichefor stem cells
Intestinal stem cells at the crypt base
Neutral competition inthe ISC niche
Paneth cellsLgr5+ stem cells
Symmetric stemcell divisions
Growth of surviving clones and extinctionof neighboring clones
Crypts inevitably drifttoward clonality
Anoikis
Nutrients
Cell amplification
Migration
PEYER’S PATCH
CRYPT
VILLUS
Lymphoid cellsLymphoid cells
EnterocytesNutrients absorption
Transient amplifying cellsProliferationLineage commitment
Paneth cellsInnate immune responseStem cell niche maintenance
Tuft cellsOpioids releaseProstanoids productionOther?
Goblet cellsMucus secretion
Enteroendocrine cellsHormone production
M cellsAntigen sampling
Intestinal stem cells (ISCs)Tissue renewal
Label retaining cells (LRCs)Paneth cell precursorsQuiescent cellsRegeneration of ISCs
The small intestine
WNTWNT
WNT
WNT
RSPO
β-cat
β-cat
NOTCHNOTCH-IC
DLL1/4
LRIG1
PA N E T HC E L L
I S C ( C B C )
ERBBProliferation
Inhibition of the secretory program: HES1Cell positioning: EPHB2
Silencing of cell-cycleinhibitors (p27kip, p57kip)
Repression of expression of Dll1/4
Proliferation, block differentiation: MYCRegulation of WNT signaling:
ZNRF3/RNF43, LGR5Cell positioning: EPHB2, EPHB3
Self-renewal: ASCL2
BMPRI
ZNRF3/RNF43
?
?
?
S T R O M A L C E L L
GREM
BMP
LGR4/5 FRIZZLEDLRP6
TCF
CSL
BMPRII
TGFα
EGF
Signaling in ISCs
SnapShot: The Intestinal CryptHans Clevers1 and Eduard Batlle2,31Hubrecht Institute, KNAW and University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, the Netherlands2Institute for Research in Biomedicine (IRB Barcelona), 08028 Barcelona, Spain3Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain
Intestinal organoids provide a convenient and physiologically relevant in vitro model system for studying the intestinal epithelium.
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IntestiCult™ Organoid Growth Medium (Mouse) (Catalog #06005)Cell culture medium for establishment and maintenance of mouse intestinal organoids
IntestiCult™ Organoid Growth Medium (Human) (Catalog #06010)Cell culture medium for establishment and maintenance of adult stem cell-derived human intestinal organoids
STEMdiff™ Intestinal Organoid Kit (Catalog #05140)Serum-free medium kit for establishment and maintenance of intestinal organoids from human pluripotent stem cells
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DOCUMENT #28227 | VERSION 1.0.3