Page last updated: 2024-10-24

intestinal stem cell homeostasis

Definition

Target type: biologicalprocess

Any biological process involved in the maintenance of the steady-state number of intestinal stem cells within a population of cells. [GOC:nhn, PMID:22042863, PMID:22608824]

Intestinal stem cell homeostasis is a tightly regulated process that ensures the continuous renewal of the intestinal epithelium. This process relies on a population of intestinal stem cells (ISCs) located at the base of the crypts of Lieberkühn, which are invaginations in the intestinal lining. ISCs possess the remarkable ability to self-renew and differentiate into all the cell types that make up the intestinal epithelium, including absorptive enterocytes, mucus-secreting goblet cells, hormone-producing enteroendocrine cells, and Paneth cells.

Paneth cells, located at the crypt base, play a crucial role in maintaining ISC niche by secreting antimicrobial peptides and growth factors, which contribute to ISC survival and proliferation. The ISC niche also comprises other cellular components, including mesenchymal cells and immune cells, which provide structural support and regulate ISC behavior.

The Wnt signaling pathway is central to ISC self-renewal and proliferation. Wnt ligands secreted from Paneth cells activate the Wnt signaling pathway within ISCs, promoting their proliferation and preventing differentiation. The Notch signaling pathway, on the other hand, regulates ISC differentiation. Notch activation triggers ISCs to differentiate into specific cell types, such as enterocytes or goblet cells.

ISCs undergo asymmetric division, resulting in one daughter cell that retains stem cell properties and another that commits to differentiation. This ensures the maintenance of the ISC pool while continuously generating differentiated cells.

The balance between ISC proliferation and differentiation is tightly regulated by various factors, including growth factors, cytokines, and mechanical cues. For example, the growth factor epidermal growth factor (EGF) promotes ISC proliferation, while transforming growth factor-beta (TGF-β) inhibits ISC proliferation and promotes differentiation.

Disruptions in intestinal stem cell homeostasis can lead to various gastrointestinal diseases, including inflammatory bowel disease (IBD), colorectal cancer, and malabsorption syndromes. The understanding of ISC biology and the intricate mechanisms that govern ISC homeostasis provides a foundation for developing novel therapeutic strategies for these diseases.'
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Proteins (3)

ProteinDefinitionTaxonomy
Nucleotide-binding oligomerization domain-containing protein 2A nucleotide-binding oligomerization domain-containing protein 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9HC29]Homo sapiens (human)
Phospholipase A2, membrane associatedA phospholipase A2, membrane associated that is encoded in the genome of human. [PRO:DNx, UniProtKB:P14555]Homo sapiens (human)
Group 10 secretory phospholipase A2A group 10 secretory phospholipase A2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O15496]Homo sapiens (human)

Compounds (27)

CompoundDefinitionClassesRoles
quinacrinequinacrine : A member of the class of acridines that is acridine substituted by a chloro group at position 6, a methoxy group at position 2 and a [5-(diethylamino)pentan-2-yl]nitrilo group at position 9.

Quinacrine: An acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years. It has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. It is used in cell biological experiments as an inhibitor of phospholipase A2.
acridines;
aromatic ether;
organochlorine compound;
tertiary amino compound
antimalarial;
EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitor
nifedipineNifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.C-nitro compound;
dihydropyridine;
methyl ester
calcium channel blocker;
human metabolite;
tocolytic agent;
vasodilator agent
paclitaxelTaxus: Genus of coniferous yew trees or shrubs, several species of which have medicinal uses. Notable is the Pacific yew, Taxus brevifolia, which is used to make the anti-neoplastic drug taxol (PACLITAXEL).taxane diterpenoid;
tetracyclic diterpenoid
antineoplastic agent;
human metabolite;
metabolite;
microtubule-stabilising agent
ubenimexubenimex: growth inhibitor
5-benzyloxytryptophan
fpl 67047xxFPL 67047XX: inhibits phospholipase A2; structure in first source
3-octylthio-1,1,1-trifluoro-2-propanone3-octylthio-1,1,1-trifluoro-2-propanone: a pesticide synergist; inhibits juvenile hormone esterase
docetaxel anhydrousdocetaxel anhydrous : A tetracyclic diterpenoid that is paclitaxel with the N-benzyloxycarbonyl group replaced by N-tert-butoxycarbonyl, and the acetoxy group at position 10 replaced by a hydroxy group.

Docetaxel: A semisynthetic analog of PACLITAXEL used in the treatment of locally advanced or metastatic BREAST NEOPLASMS and NON-SMALL CELL LUNG CANCER.
secondary alpha-hydroxy ketone;
tetracyclic diterpenoid
antimalarial;
antineoplastic agent;
photosensitizing agent
varespladibaromatic ether;
benzenes;
dicarboxylic acid monoamide;
indoles;
monocarboxylic acid;
primary carboxamide
anti-inflammatory drug;
antidote;
EC 3.1.1.4 (phospholipase A2) inhibitor
ly 311727LY 311727: a potent & selective inhibitor of human non-pancreatic secretory phospholipase A2; structure given in first source
muramyl dipeptideglycopeptideimmunological adjuvant
3-methyl-7-pentyl-8-(2-phenylethylthio)purine-2,6-dioneoxopurine
3-methyl-7-(phenylmethyl)-8-(propan-2-ylthio)purine-2,6-dioneoxopurine
1-(4-methylphenyl)sulfonyl-2-benzimidazolaminesulfonamide
1-(4-chlorophenyl)sulfonyl-2-benzimidazolaminesulfonamide
1-(benzenesulfonyl)-2-benzimidazolaminesulfonamide
1-(4-nitrophenyl)sulfonyl-2-benzimidazolaminesulfonamide
amentoflavonebiflavonoid;
hydroxyflavone;
ring assembly
angiogenesis inhibitor;
antiviral agent;
cathepsin B inhibitor;
P450 inhibitor;
plant metabolite
pd 166285
ochnaflavoneochnaflavone : A biflavonoid with an ether linkage between the B-rings of the apigenin and luteolin subunits. It has been isolated from several members of the Ochnaceae plant family.

ochnaflavone: from Lonicera japonica; structure given in first source
aromatic ether;
biflavonoid;
hydroxyflavone
anti-inflammatory agent;
antiatherogenic agent;
antibacterial agent;
EC 3.1.1.4 (phospholipase A2) inhibitor;
leukotriene antagonist;
plant metabolite
manoalidemanoalide : A sesterterpenoid isolated from the marine sponge Luffariella variabilis and which has been shown to exhibit inhibitory activity towards phospholipase A2.

manoalide: phospholipase A2 inhibitor; sesterterpene from marine sponge L. variabilis; structure given in first source
butenolide;
lactol;
sesterterpenoid
EC 3.1.1.4 (phospholipase A2) inhibitor;
EC 5.99.1.2 (DNA topoisomerase) inhibitor;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
metabolite
ym 26734YM 26734: inhibits group II phospholipase A2; structure given in first source
indoxamindoxam: structure in first source
bolinaquinonebolinaquinone: a marine sesquiterpenoid from sponge Dysidea sp. with anti-inflammatory activity; structure in first source
cacospongionolide bcacospongionolide B: isolated from the sponge Fasciospongia cavernosa; structure in first source
1-(4-methoxyphenyl)sulfonyl-2-benzimidazolaminesulfonamide
5,6-dimethyl-1-(4-methylphenyl)sulfonyl-2-benzimidazolaminesulfonamide