Page last updated: 2024-10-24

positive regulation of stem cell differentiation

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of stem cell differentiation. [GOC:obol]

Positive regulation of stem cell differentiation is a complex and tightly controlled process that governs the transition of undifferentiated stem cells into specialized cell types. This process is essential for tissue development, regeneration, and homeostasis. It involves a series of molecular events that orchestrate changes in gene expression, cellular signaling pathways, and epigenetic modifications, ultimately leading to the acquisition of specific cell fates.

**Key factors involved in positive regulation of stem cell differentiation:**

* **Transcription factors:** These proteins bind to specific DNA sequences and regulate gene expression, promoting the expression of genes required for differentiation. Examples include Oct4, Sox2, Nanog, and Klf4, which are essential for maintaining stem cell pluripotency, and lineage-specific transcription factors that drive differentiation towards specific cell types.
* **Signaling pathways:** Cell-cell interactions and environmental cues activate signaling pathways that regulate stem cell behavior. Examples include Wnt, Notch, TGF-β, and Hedgehog pathways, which can act as both positive and negative regulators of differentiation, depending on the specific context.
* **Epigenetic modifications:** These changes in chromatin structure and DNA methylation patterns influence gene expression, allowing for stable and heritable alterations in cell fate. Examples include histone modifications, such as acetylation and methylation, which can regulate gene accessibility, and DNA methylation, which can silence or activate genes.
* **Extracellular matrix:** The surrounding environment, including the extracellular matrix, provides physical and chemical cues that guide stem cell differentiation. This includes factors like adhesion molecules and growth factors that can influence cell fate decisions.
* **Microenvironment:** The stem cell niche, a specialized microenvironment within tissues, provides a supportive environment for stem cell maintenance and differentiation. This niche contains specific cell types, signaling molecules, and structural components that regulate stem cell behavior.

**Steps involved in positive regulation of stem cell differentiation:**

1. **Initiation:** Stem cells receive signals from their microenvironment or developmental cues that trigger the differentiation process. These signals can be in the form of growth factors, cytokines, or changes in the extracellular matrix.
2. **Commitment:** Stem cells commit to a specific lineage, becoming restricted in their developmental potential. This commitment involves changes in gene expression patterns, leading to the activation of lineage-specific transcription factors and the silencing of genes associated with pluripotency.
3. **Differentiation:** Committed stem cells undergo a series of morphological and functional changes, acquiring the characteristics of the target cell type. This includes changes in cell shape, size, and expression of cell-type-specific proteins.
4. **Maturation:** Differentiated cells undergo further maturation, acquiring their final functional state and integrating into the appropriate tissue or organ.

**Regulation of positive regulation of stem cell differentiation:**

* **Intrinsic factors:** Stem cells possess an internal program that governs their differentiation potential. This program is influenced by factors such as cell cycle control, telomere length, and the expression of specific genes.
* **Extrinsic factors:** The environment surrounding stem cells plays a crucial role in regulating their differentiation. This includes factors like growth factors, cytokines, extracellular matrix components, and interactions with other cells.

**Importance of positive regulation of stem cell differentiation:**

* **Tissue development:** Proper stem cell differentiation is essential for the development and maintenance of all tissues and organs during embryonic development.
* **Tissue regeneration:** Stem cells are responsible for repairing and regenerating tissues after injury or disease.
* **Homeostasis:** Stem cells maintain tissue homeostasis by replenishing cells that are lost due to normal wear and tear.

In summary, positive regulation of stem cell differentiation is a complex process that involves a coordinated interplay of intrinsic and extrinsic factors, leading to the production of specialized cell types that are essential for tissue development, regeneration, and homeostasis.'
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Proteins (2)

ProteinDefinitionTaxonomy
NAD-dependent protein deacetylase sirtuin-6An NAD-dependent protein deacylase sirtuin-6 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8N6T7]Homo sapiens (human)
Fibroblast growth factor 2A fibroblast growth factor 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P09038]Homo sapiens (human)

Compounds (12)

CompoundDefinitionClassesRoles
niacinamidenicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group.pyridine alkaloid;
pyridinecarboxamide;
vitamin B3
anti-inflammatory agent;
antioxidant;
cofactor;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
EC 3.5.1.98 (histone deacetylase) inhibitor;
Escherichia coli metabolite;
geroprotector;
human urinary metabolite;
metabolite;
mouse metabolite;
neuroprotective agent;
Saccharomyces cerevisiae metabolite;
Sir2 inhibitor
pyrazinamidepyrazinecarboxamide : A monocarboxylic acid amide resulting from the formal condensation of the carboxy group of pyrazinoic acid (pyrazine-2-carboxylic acid) with ammonia. A prodrug for pyrazinoic acid, pyrazinecarboxamide is used as part of multidrug regimens for the treatment of tuberculosis.monocarboxylic acid amide;
N-acylammonia;
pyrazines
antitubercular agent;
prodrug
pyrazinoic acidpyrazine-2-carboxylic acid : The parent compound of the class of pyrazinecarboxylic acids, that is pyrazine bearing a single carboxy substituent. The active metabolite of the antitubercular drug pyrazinamide.

pyrazinoic acid: active metabolite of pyrazinamide; structure
pyrazinecarboxylic acidantitubercular agent;
drug metabolite
1-(4-nitrophenyl)piperazine1-(4-nitrophenyl)piperazine: structure in first source
rubimaillinrubimaillin : A benzochromene that is 2H-benzo[h]chromene which is substituted by two methyl groups at position 2, a methoxycarbonyl group at position 5, and a hydroxy group at position 6. Found in the Chinese medical plant Rubia cordifola, It has an anti-cancer effect by inhibition of TNF-alpha-induced NF-kappaB activation. It is also a dual inhibitor of acyl-CoA:cholesterol acyltransferase 1 and 2 (ACAT1 and ACAT2), but is more selective for the ACAT2 isozyme.

rubimaillin: structure given in first source
benzochromene;
methyl ester;
phenols
acyl-CoA:cholesterol acyltransferase 2 inhibitor;
anti-inflammatory agent;
antineoplastic agent;
apoptosis inducer;
neuroprotective agent;
NF-kappaB inhibitor;
plant metabolite
5-chloropyrazinamide
trichostatin atrichostatin A: chelates zinc ion in the active site of histone deacetylases, resulting in preventing histone unpacking so DNA is less available for transcription; do not confuse with TRICHOSANTHIN which is a protein; found in STREPTOMYCESantibiotic antifungal agent;
hydroxamic acid;
trichostatin
bacterial metabolite;
EC 3.5.1.98 (histone deacetylase) inhibitor;
geroprotector
(3R,5S)-fluvastatin(3R,5S)-fluvastatin : A (6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid diastereoisomer in which the stereocentres beta- and delta- to the carboxy group have R and S configuration, respectively. The drug fluvastatin is an equimolar mixture of this compound and its enantiomer.(6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid;
statin (synthetic)
tivozanibN-(2-chloro-4-((6,7-dimethoxy-4-quinolyl)oxy)phenyl)-N'-(5-methyl-3-isoxazolyl)urea: KNR-951 is the HCl, monohydrate salt; an antineoplastic agent; structure in first sourcearomatic ether
ly2784544pyridazines
phosphomannopentaose sulfatephosphomannopentaose sulfate: structure in first source
pg 545PG 545: an anti-angiogenesis agent with heparanase inhibitory activity; structure in first source