LKB1 Represses ATOH1 via PDK4 and Energy Metabolism and Regulates Intestinal Stem Cell Fate.
AMP-Activated Protein Kinase Kinases
AMP-Activated Protein Kinases
/ genetics
Animals
Basic Helix-Loop-Helix Transcription Factors
/ genetics
Cell Differentiation
/ drug effects
Cell Line, Tumor
Dichloroacetic Acid
/ pharmacology
Energy Metabolism
/ physiology
Gene Knockdown Techniques
HEK293 Cells
Humans
Intestinal Mucosa
/ cytology
Intestine, Small
/ cytology
Mice
Mice, Knockout
Primary Cell Culture
Protein Serine-Threonine Kinases
/ genetics
Pyruvate Dehydrogenase Acetyl-Transferring Kinase
/ antagonists & inhibitors
RNA, Messenger
/ metabolism
RNA, Small Interfering
/ metabolism
RNA-Seq
Stem Cells
/ physiology
Transcription, Genetic
Up-Regulation
/ drug effects
DCA
Gene Regulation
Mitochondria
Renewal
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
03
04
2019
revised:
02
12
2019
accepted:
30
12
2019
pubmed:
14
1
2020
medline:
11
7
2020
entrez:
14
1
2020
Statut:
ppublish
Résumé
In addition to the Notch and Wnt signaling pathways, energy metabolism also regulates intestinal stem cell (ISC) function. Tumor suppressor and kinase STK11 (also called LKB1) regulates stem cells and cell metabolism. We investigated whether loss of LKB1 alters ISC homeostasis in mice. We deleted LKB1 from ISCs in mice using Lgr5-regulated CRE-ERT2 (Lkb1 Some intestinal crypts from Lkb1 LKB1 represses transcription of ATOH1, via PDK4, in ISCs, restricting their differentiation into secretory lineages. These findings provide a connection between metabolism and the fate determination of ISCs.
Sections du résumé
BACKGROUND & AIMS
In addition to the Notch and Wnt signaling pathways, energy metabolism also regulates intestinal stem cell (ISC) function. Tumor suppressor and kinase STK11 (also called LKB1) regulates stem cells and cell metabolism. We investigated whether loss of LKB1 alters ISC homeostasis in mice.
METHODS
We deleted LKB1 from ISCs in mice using Lgr5-regulated CRE-ERT2 (Lkb1
RESULTS
Some intestinal crypts from Lkb1
CONCLUSIONS
LKB1 represses transcription of ATOH1, via PDK4, in ISCs, restricting their differentiation into secretory lineages. These findings provide a connection between metabolism and the fate determination of ISCs.
Identifiants
pubmed: 31930988
pii: S0016-5085(20)30072-X
doi: 10.1053/j.gastro.2019.12.033
pii:
doi:
Substances chimiques
ATOH1 protein, human
0
Atoh1 protein, mouse
0
Basic Helix-Loop-Helix Transcription Factors
0
Pdk4 protein, mouse
0
Pyruvate Dehydrogenase Acetyl-Transferring Kinase
0
RNA, Messenger
0
RNA, Small Interfering
0
Dichloroacetic Acid
9LSH52S3LQ
Protein Serine-Threonine Kinases
EC 2.7.11.1
STK11 protein, human
EC 2.7.11.1
Stk11 protein, mouse
EC 2.7.11.1
AMP-Activated Protein Kinase Kinases
EC 2.7.11.3
AMP-Activated Protein Kinases
EC 2.7.11.31
PRKAA1 protein, human
EC 2.7.11.31
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1389-1401.e10Informations de copyright
Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.