Stem cell fate determination through protein O-GlcNAcylation

Autor: Bright Starling Emerald, Muhammad Abid Sheikh, Suraiya A. Ansari
Rok vydání: 2021
Předmět:
0301 basic medicine
MSCs
mesenchymal stem cells
TET
ten-eleven translocation
Biochemistry
Epigenesis
Genetic
O-GlcNAcylation
hPSCs
human pluripotent stem cells
Gene Regulatory Networks
NTDs
neural tube defects
SAM
S-adenosyl methionine
Induced pluripotent stem cell
Uridine Diphosphate N-Acetylglucosamine
Stem Cells
iPSCs
induced pluripotent stem cells
Cell biology
NDDs
neurodevelopmental disorders
Stem cell fate commitment
Stem cell
transcription
MHC
myosin heavy chain
Adult stem cell
Reviews
PPP
pentose phosphate pathway
PTM
posttranslational modifications
Cell fate determination
Biology
MAP2
microtubule-associated protein 2
03 medical and health sciences
ROS
reactive oxygen species
SOD
superoxide dismutase
Animals
Humans
Cell Lineage
Epigenetics
Molecular Biology
epigenetics
DON
6-diazo-5-oxo-norleucine
030102 biochemistry & molecular biology
HSCs
hematopoietic stem cells
Proteins
ESCs
embryonic stem cells
OGT
O-GlcNAc transferase
Cell Biology
Embryonic stem cell
HBP
hexosamine biosynthesis pathway
030104 developmental biology
Stem cell fate determination
OGA
O-GlcNAcase
gene expression
cell fate determination
ODD
oxygen-dependent degradation
Protein Processing
Post-Translational
Zdroj: The Journal of Biological Chemistry
ISSN: 0021-9258
DOI: 10.1074/jbc.rev120.014915
Popis: Embryonic and adult stem cells possess the capability of self-renewal and lineage-specific differentiation. The intricate balance between self-renewal and differentiation is governed by developmental signals and cell-type-specific gene regulatory mechanisms. A perturbed intra/extracellular environment during lineage specification could affect stem cell fate decisions resulting in pathology. Growing evidence demonstrates that metabolic pathways govern epigenetic regulation of gene expression during stem cell fate commitment through the utilization of metabolic intermediates or end products of metabolic pathways as substrates for enzymatic histone/DNA modifications. UDP-GlcNAc is one such metabolite that acts as a substrate for enzymatic mono-glycosylation of various nuclear, cytosolic, and mitochondrial proteins on serine/threonine amino acid residues, a process termed protein O-GlcNAcylation. The levels of GlcNAc inside the cells depend on the nutrient availability, especially glucose. Thus, this metabolic sensor could modulate gene expression through O-GlcNAc modification of histones or other proteins in response to metabolic fluctuations. Herein, we review evidence demonstrating how stem cells couple metabolic inputs to gene regulatory pathways through O-GlcNAc-mediated epigenetic/transcriptional regulatory mechanisms to govern self-renewal and lineage-specific differentiation programs. This review will serve as a primer for researchers seeking to better understand how O-GlcNAc influences stemness and may catalyze the discovery of new stem-cell-based therapeutic approaches.
Databáze: OpenAIRE
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