negative regulation of hematopoietic stem cell differentiation
Definition
Target type: biologicalprocess
Any process that stops, prevents or reduces the frequency, rate or extent of hematopoietic stem cell differentiation. [GOC:TermGenie, PMID:23403623]
Negative regulation of hematopoietic stem cell differentiation is a complex and tightly regulated process that ensures the proper balance between self-renewal and differentiation of hematopoietic stem cells (HSCs). HSCs are the primary source of all blood cells, and their ability to differentiate into specific lineages is essential for maintaining normal blood cell production. Negative regulation of HSC differentiation is critical for preventing premature depletion of the HSC pool and maintaining its long-term regenerative capacity. This intricate process involves a diverse array of signaling pathways, transcription factors, and epigenetic modifications that act in concert to modulate the expression of genes involved in cell fate determination.
One of the key mechanisms involved in negative regulation of HSC differentiation is the suppression of pro-differentiation signals. These signals are often mediated by cytokines, growth factors, or signaling molecules that promote the commitment of HSCs to specific lineages. For example, the cytokine thrombopoietin (TPO) is known to stimulate megakaryocyte differentiation, while granulocyte colony-stimulating factor (G-CSF) promotes neutrophil differentiation. Negative regulation of HSC differentiation can involve blocking these pro-differentiation signals through various mechanisms such as inhibiting the binding of cytokines to their receptors, downregulating the expression of signaling molecules, or activating downstream signaling pathways that counteract the effects of pro-differentiation signals.
Another crucial mechanism is the activation of signaling pathways that promote HSC self-renewal. These pathways often involve transcription factors and epigenetic modifications that maintain the undifferentiated state of HSCs. For instance, the transcription factor Oct4 is a key regulator of stem cell pluripotency, and its expression is tightly regulated in HSCs. Other transcription factors, such as HOX genes, are also involved in maintaining the HSC pool by regulating the expression of genes involved in cell cycle control and differentiation. Epigenetic modifications, such as histone acetylation and DNA methylation, play a crucial role in regulating gene expression during HSC differentiation. Negative regulation of HSC differentiation can involve maintaining a specific epigenetic landscape that favors self-renewal over differentiation.
The intricate interplay between these signaling pathways, transcription factors, and epigenetic modifications ensures that HSCs maintain their self-renewal capacity while also allowing for controlled differentiation into various blood cell lineages. Disruptions in these regulatory mechanisms can lead to various hematological disorders, highlighting the importance of tightly regulating HSC differentiation.'
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Proteins (2)
| Protein | Definition | Taxonomy |
|---|---|---|
| Nuclear factor erythroid 2-related factor 2 | A nuclear factor erythroid 2-related factor 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q16236] | Homo sapiens (human) |
| Stress-70 protein, mitochondrial | A stress-70 protein, mitochondrial that is encoded in the genome of human. [PRO:DAN] | Homo sapiens (human) |
Compounds (23)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| melatonin | acetamides; tryptamines | anticonvulsant; central nervous system depressant; geroprotector; hormone; human metabolite; immunological adjuvant; mouse metabolite; radical scavenger | |
| sulforaphane | sulforaphane : An isothiocyanate having a 4-(methylsulfinyl)butyl group attached to the nitrogen. sulforaphane: from Cardaria draba L. | isothiocyanate; sulfoxide | antineoplastic agent; antioxidant; EC 3.5.1.98 (histone deacetylase) inhibitor; plant metabolite |
| dimethylformamide | Dimethylformamide: A formamide in which the amino hydrogens are replaced by methyl groups. N,N-dimethylformamide : A member of the class of formamides that is formamide in which the amino hydrogens are replaced by methyl groups. | formamides; volatile organic compound | geroprotector; hepatotoxic agent; polar aprotic solvent |
| iberin | isothiocyanate; sulfoxide | apoptosis inducer; plant metabolite; quorum sensing inhibitor | |
| oleanolic acid | hydroxy monocarboxylic acid; pentacyclic triterpenoid | plant metabolite | |
| 2-tert-butylhydroquinone | 2-tert-butylhydroquinone : A member of the class of hydroquinones in which one of the ring hydrogens of hydroquinone is replaced by a tert-butyl group. 2-tert-butylhydroquinone: an anticarcinogenic and chemopreventive agent | hydroquinones | food antioxidant |
| brusatol | brusatol: quassinoid from B. javanica; structure | triterpenoid | |
| hei 712 | organofluorine compound; quinolone | ||
| 2-(5-Chlorobenzo[b]thiophen-3-yl)acetic acid | 1-benzothiophenes | ||
| alyssin | sulfoxide | ||
| bardoxolone methyl | methyl 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate: structure in first source | cyclohexenones | |
| resveratrol | trans-resveratrol : A resveratrol in which the double bond has E configuration. | resveratrol | antioxidant; phytoalexin; plant metabolite; quorum sensing inhibitor; radical scavenger |
| dimethyl fumarate | diester; enoate ester; methyl ester | antipsoriatic; immunomodulator | |
| (1e,4e)-1,5-bis(2-methoxyphenyl)penta-1,4-dien-3-one | |||
| curcumin | curcumin : A beta-diketone that is methane in which two of the hydrogens are substituted by feruloyl groups. A natural dyestuff found in the root of Curcuma longa. Curcumin: A yellow-orange dye obtained from tumeric, the powdered root of CURCUMA longa. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes. | aromatic ether; beta-diketone; diarylheptanoid; enone; polyphenol | anti-inflammatory agent; antifungal agent; antineoplastic agent; biological pigment; contraceptive drug; dye; EC 1.1.1.205 (IMP dehydrogenase) inhibitor; EC 1.1.1.21 (aldehyde reductase) inhibitor; EC 1.1.1.25 (shikimate dehydrogenase) inhibitor; EC 1.6.5.2 [NAD(P)H dehydrogenase (quinone)] inhibitor; EC 1.8.1.9 (thioredoxin reductase) inhibitor; EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor; EC 3.5.1.98 (histone deacetylase) inhibitor; flavouring agent; food colouring; geroprotector; hepatoprotective agent; immunomodulator; iron chelator; ligand; lipoxygenase inhibitor; metabolite; neuroprotective agent; nutraceutical; radical scavenger |
| umi-77 | UMI-77: an Mcl-1 inhibitor; structure in first source | ||
| 2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone | 2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone: an anti-inflammatory agent that down-regulates cyclooxygenase-2 expression; structure in first source | ||
| strigol | strigol : A strigolactone in which the tricyclic lactone moiety bears a hydroxy substitutuent at the position para to the gem-dimethyl group. strigol: a strigolactone from roots of various PLANTS; it stimulates seed germination of parasitic STRIGA and OROBANCHE; structure in first source | indenofuran; secondary alcohol; strigolactone | |
| hylin | |||
| 6-methylsulfinylhexyl isothiocyanate | 6-(Methylsulfinyl)hexyl isothiocyanate: showed a dose-dependent inhibition of LPS-induced nitric oxide (NO), iNOS mRNA and protein. | sulfoxide | |
| (((4-nitrophenyl)amino)(2,2,4,4-tetramethyl thiochroman-6-yl)amino) methane-1-thione | |||
| dimethoxycurcumin | dimethoxycurcumin: has antineoplsatic activity; structure in first source | ||
| (1S,2R)-2-[[(1S)-1-[(1,3-dioxo-2-isoindolyl)methyl]-3,4-dihydro-1H-isoquinolin-2-yl]-oxomethyl]-1-cyclohexanecarboxylic acid | LH601A: inhibits the interaction between KEAP1 and NRF2; structure in first source | phthalimides |