Modulation of stem cell fate in intestinal homeostasis, injury and repair

Table 1 Apoptosis regulation of intestinal stem cells

Biological process or signaling	Molecule	Role	Evidence
Mitochondrial dysfunction	Puma	Pro-apoptotic	Puma depletion reduces chemoradiotherapy- induced apoptosis in a p53-dependent manner[102,136]
	Bcl-2	Anti-apoptotic	Bcl-2 is highly expressed in ISCs and alleviating radiation-induced damage[137]
	Survivin	Anti-apoptotic	An essential guardian of ISC during mucosal healing[138]
	PRPS1	Pro-apoptotic	PRPS1 deficiency exhibit resistance against intestinal damage in a manner dependent upon Lgr5+ ISCs[139]
Immune response	IL-22	Anti-apoptotic	IL-22 deficiency led to increased crypt apoptosis, depletion of ISCs[97]
	NOD2	Anti-apoptotic	Nod2 stimulation triggers stem cell survival against oxidative stress-mediated cell death[93]
Hippo	YAP	Anti-apoptotic	Loss of YAP activity results in sensitivity of crypt stem cells to apoptosis and reduced cell proliferation during regeneration[140]
GPCR	β-Arrestin1/2	Anti-apoptotic	βArr reduced the chemotherapy- induced Lgr5+ stem cell apoptosis by inhibiting endoplasmic reticulum stress[141,142]
Hormone	GLP-2	Anti-apoptotic	GLP-2 expanded intestinal organoids and downregulated apoptosis-related genes[143]
	Ghrelin	Anti-apoptotic	Ghrelin treatment accelerated the reversal of radiation-induced epithelial damage and defective self-renewing property of ISCs[144]
Methylation	Mettl14	Anti-apoptotic	Specific deletion of the Mettl14 gene resulted in colonic stem cell apoptosis[145]
	GsdmC	Anti-apoptotic	GsdmC N6-adenomethylation protects mitochondrial homeostasis and is essential for Lgr5+ cell survival[146]
Glycosylation	HYOU1	Anti-apoptotic	HYOU1 glycosylation modulated by FUT2 protects ISCs against apoptosis[147]

ISCs: Intestinal stem cells; PRPS1: Phosphoribosyl pyrophosphate synthetase 1; GPCR: G protein coupled receptor.