Target type: biologicalprocess
Any process that activates or increases the frequency, rate or extent of hematopoietic stem cell migration. [GOC:obol]
Positive regulation of hematopoietic stem cell migration is a complex process involving a tightly regulated interplay of signaling pathways, adhesion molecules, and chemokines. Hematopoietic stem cells (HSCs) reside in specific niches within the bone marrow, where they are maintained in a quiescent state. Upon receiving appropriate signals, HSCs initiate migration from their niche to the peripheral blood, where they differentiate into various blood cell types. The process of positive regulation of HSC migration involves several key steps:
**1. Chemokine Signaling:**
- Chemokines, a family of small signaling proteins, play a crucial role in attracting HSCs towards specific destinations.
- Chemokines bind to chemokine receptors expressed on HSCs, triggering downstream signaling cascades.
- These cascades activate intracellular pathways, such as the PI3K/AKT pathway, which promote cell survival, proliferation, and migration.
- Specific chemokines, such as CXCL12, SDF-1, and CXCL13, have been shown to regulate HSC migration in the bone marrow.
**2. Adhesion Molecule Interactions:**
- HSCs interact with their niche through a variety of adhesion molecules, such as integrins, selectins, and cadherins.
- These molecules mediate cell-cell and cell-matrix interactions, providing anchorage and stability to HSCs within the niche.
- During migration, HSCs detach from the niche by modulating the expression and activity of these adhesion molecules.
**3. Cytoskeletal Rearrangement:**
- Migration of HSCs requires dynamic changes in their cytoskeleton, the network of proteins that provides structural support to the cell.
- Actin polymerization and depolymerization are crucial for cell motility, allowing HSCs to extend protrusions (lamellipodia and filopodia) and move forward.
**4. Signaling Pathways Involved in HSC Migration:**
- Multiple signaling pathways, including the PI3K/AKT, Wnt, Notch, and Hedgehog pathways, are involved in regulating HSC migration.
- These pathways converge on key downstream targets, such as transcription factors, which control the expression of genes involved in migration and differentiation.
**5. Microenvironment Modulation:**
- The microenvironment surrounding HSCs, including the extracellular matrix, stromal cells, and other immune cells, plays a critical role in regulating their migration.
- Cells within the niche release growth factors and cytokines that influence HSC behavior, promoting or inhibiting their migration.
**6. Regulation of Gene Expression:**
- Migration of HSCs is tightly controlled by the expression of specific genes involved in cell adhesion, motility, and signaling.
- Transcription factors, such as GATA1, PU.1, and RUNX1, regulate the expression of these genes, fine-tuning HSC migration and differentiation.
In summary, positive regulation of hematopoietic stem cell migration is a complex and finely tuned process involving multiple signaling pathways, adhesion molecules, cytoskeletal dynamics, and microenvironmental cues. Understanding the molecular mechanisms underlying this process is crucial for developing therapeutic strategies for blood disorders and for promoting HSC transplantation.'
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Protein | Definition | Taxonomy |
---|---|---|
C-C chemokine receptor type 2 | A C-C chemokine receptor type 2 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P41597] | Homo sapiens (human) |
Receptor-type tyrosine-protein phosphatase C | A receptor-type tyrosine-protein phosphatase C that is encoded in the genome of human. [PRO:CNA, UniProtKB:P08575] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
4-hydroxyphenylglyoxylic acid | 4-hydroxyphenylglyoxylate : Conjugate base of 4-hydroxyphenylglyoxylic acid. 4-hydroxyphenylglyoxylic acid: RN given refers to parent cpd | phenols | |
5-iodo-2-(oxaloamino)benzoic acid | organoiodine compound | ||
amiodarone | amiodarone : A member of the class of 1-benzofurans that is 1-benzofuran substituted by a butyl group at position 2 and a 4-[2-(diethylamino)ethoxy]-3,5-diiodobenzoyl group at position 3. It is a cardiovascular drug used for the treatment of cardiac dysrhythmias. Amiodarone: An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance. | 1-benzofurans; aromatic ketone; organoiodine compound; tertiary amino compound | cardiovascular drug |
disulfiram | organic disulfide; organosulfur acaricide | angiogenesis inhibitor; antineoplastic agent; apoptosis inducer; EC 1.2.1.3 [aldehyde dehydrogenase (NAD(+))] inhibitor; EC 3.1.1.1 (carboxylesterase) inhibitor; EC 3.1.1.8 (cholinesterase) inhibitor; EC 5.99.1.2 (DNA topoisomerase) inhibitor; ferroptosis inducer; fungicide; NF-kappaB inhibitor | |
fasudil | fasudil : An isoquinoline substituted by a (1,4-diazepan-1-yl)sulfonyl group at position 5. It is a Rho-kinase inhibitor and its hydrochloride hydrate form is approved for the treatment of cerebral vasospasm and cerebral ischemia. fasudil: intracellular calcium antagonist; structure in first source | isoquinolines; N-sulfonyldiazepane | antihypertensive agent; calcium channel blocker; EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor; geroprotector; neuroprotective agent; nootropic agent; vasodilator agent |
nifedipine | Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. | C-nitro compound; dihydropyridine; methyl ester | calcium channel blocker; human metabolite; tocolytic agent; vasodilator agent |
9,10-phenanthrenequinone | 9,10-phenanthrenequinone: structure | phenanthrenes | |
dibenzothiazyl disulfide | dibenzothiazol-2-yl disulfide : An organic disulfide resulting from the formal oxidative coupling of the thiol groups of two molecules of 1,3-benzothiazole-2-thiol. It is used as an accelerator in the rubber industry. dibenzothiazyl disulfide: vulcanizing accelerant | benzothiazoles; organic disulfide | allergen |
oleanolic acid | hydroxy monocarboxylic acid; pentacyclic triterpenoid | plant metabolite | |
1,2-naphthoquinone | 1,2-naphthoquinone : The parent structure of the family of 1,2-naphthoquinones, in which the oxo groups of the quinone moiety are at positions 1 and 2 of the naphthalene ring. It is a metabolite of naphthalene and is found in diesel exhaust particles. naphthalene-1,2-dione: structure given in first source | 1,2-naphthoquinones | aryl hydrocarbon receptor agonist; carcinogenic agent |
1-naphthylisothiocyanate | 1-Naphthylisothiocyanate: A tool for the study of liver damage which causes bile stasis and hyperbilirubinemia acutely and bile duct hyperplasia and biliary cirrhosis chronically, with changes in hepatocyte function. It may cause skin and kidney damage. | isothiocyanate | insecticide |
plerixafor | plerixafor : An azamacrocycle consisting of two cyclam rings connected by a 1,4-phenylenebis(methylene) linker. It is a CXCR4 chemokine receptor antagonist and a hematopoietic stem cell mobilizer. It is used in combination with grulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the perpheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma. plerixafor: a bicyclam derivate, highly potent & selective inhibitor of HIV-1 & HIV-2 | azacycloalkane; azamacrocycle; benzenes; crown amine; secondary amino compound; tertiary amino compound | anti-HIV agent; antineoplastic agent; C-X-C chemokine receptor type 4 antagonist; immunological adjuvant |
rosiglitazone | aminopyridine; thiazolidinediones | EC 6.2.1.3 (long-chain-fatty-acid--CoA ligase) inhibitor; ferroptosis inhibitor; insulin-sensitizing drug | |
cryptotanshinone | cryptotanshinone: from Salvia miltiorrhiza | abietane diterpenoid | anticoronaviral agent |
fasudil hydrochloride | fasudil hydrochloride : A hydrochloride obtained by reaction of fasudil with one equivalent of hydrochloric acid. | hydrochloride | antihypertensive agent; calcium channel blocker; EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor; neuroprotective agent; nootropic agent; vasodilator agent |
tak 779 | |||
2-(oxaloamino)benzoic acid | (oxaloamino)benzoic acid | ||
illudalic acid | illudalic acid: isolated from Clitocybe illudens; structure in first source | ||
bay 11-7085 | BAY11-7085 : A sulfone that is benzene substituted by [(E)-2-cyanoethenyl]sulfonyl and tert-butyl groups at position 1 and 4, respectively. It is an irreversible inhibitor of IkappaB-alpha phosphorylation in cells (IC50 = 10 muM) and prevents the activation of NF-kappaB. | benzenes; nitrile; sulfone | anti-inflammatory agent; antibacterial agent; antineoplastic agent; apoptosis inducer; autophagy inducer; EC 2.7.11.10 (IkappaB kinase) inhibitor; ferroptosis inducer; NF-kappaB inhibitor |
ucb 35625 | UCB 35625: J-113863 is the (trans)-isomer; structure in first source | ||
rs 504393 | RS 504393: structure in first source | 1,3-oxazoles | |
incb3344 | INCB3344: potent and selective small molecule CCR2 chemokine receptor antagonist | ||
amd 070 | mavorixafor: a derivative of AMD3100; a CXCR4 blocker | aminoquinoline | |
cenicriviroc | cenicriviroc : A member of the class of benzazocines that is (5Z)-1,2,3,4-tetrahydro-1-benzazocine which is substituted by a 2-methylpropyl, N-{4-[(S)-(1-propyl-1H-imidazol-5-yl)methanesulfinyl]phenyl}carboxamide and 4-(2-butoxyethoxy)phenyl groups at positions 1, 5 and 8, respectively. It is a potent chemokine 2 and 5 receptor antagonist currently in development for the treatment of liver fibrosis in adults with nonalcoholic steatohepatitis (NASH). cenicriviroc: an inhibitor of HIV-1 | aromatic ether; benzazocine; diether; imidazoles; secondary carboxamide; sulfoxide | anti-HIV agent; anti-inflammatory agent; antirheumatic drug; chemokine receptor 2 antagonist; chemokine receptor 5 antagonist |
incb 3284 | INCB 3284: a CCR2 receptor antagonist | ||
azd8309 | AZD8309: CXCR2 inhibitor | ||
3-(1-(3-(biphenyl-4-ylamino)-3-oxopropyl)-1h-1,2,3-triazol-4-yl)-6-hydroxy-1-methyl-2-phenyl-1h-indole-5-carboxylic acid | 3-(1-(3-(biphenyl-4-ylamino)-3-oxopropyl)-1H-1,2,3-triazol-4-yl)-6-hydroxy-1-methyl-2-phenyl-1H-indole-5-carboxylic acid: an SHP2 inhibitor; structure in first source | ||
n-(carbamoylmethyl)-3-trifluoromethyl benzamido-4-chlorobenzyl 3-aminopyrrolidine | |||
variabilin | variabilin: an RGD-containing antagonist of glycoprotein IIb-IIIa from the hard tick, Dermacentor variabilis; amino acid sequence given in first source |