Page last updated: 2024-10-24

positive regulation of hematopoietic stem cell migration

Definition

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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Proteins (2)

ProteinDefinitionTaxonomy
C-C chemokine receptor type 2A 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 CA receptor-type tyrosine-protein phosphatase C that is encoded in the genome of human. [PRO:CNA, UniProtKB:P08575]Homo sapiens (human)

Compounds (29)

CompoundDefinitionClassesRoles
4-hydroxyphenylglyoxylic acid4-hydroxyphenylglyoxylate : Conjugate base of 4-hydroxyphenylglyoxylic acid.

4-hydroxyphenylglyoxylic acid: RN given refers to parent cpd
phenols
5-iodo-2-(oxaloamino)benzoic acidorganoiodine compound
amiodaroneamiodarone : 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
disulfiramorganic 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
fasudilfasudil : 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
nifedipineNifedipine: 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-phenanthrenequinone9,10-phenanthrenequinone: structurephenanthrenes
dibenzothiazyl disulfidedibenzothiazol-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 acidhydroxy monocarboxylic acid;
pentacyclic triterpenoid
plant metabolite
1,2-naphthoquinone1,2-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-naphthoquinonesaryl hydrocarbon receptor agonist;
carcinogenic agent
1-naphthylisothiocyanate1-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.isothiocyanateinsecticide
plerixaforplerixafor : 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
rosiglitazoneaminopyridine;
thiazolidinediones
EC 6.2.1.3 (long-chain-fatty-acid--CoA ligase) inhibitor;
ferroptosis inhibitor;
insulin-sensitizing drug
cryptotanshinonecryptotanshinone: from Salvia miltiorrhizaabietane diterpenoidanticoronaviral agent
fasudil hydrochloridefasudil hydrochloride : A hydrochloride obtained by reaction of fasudil with one equivalent of hydrochloric acid.hydrochlorideantihypertensive 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 acidilludalic acid: isolated from Clitocybe illudens; structure in first source
bay 11-7085BAY11-7085 : 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 35625UCB 35625: J-113863 is the (trans)-isomer; structure in first source
rs 504393RS 504393: structure in first source1,3-oxazoles
incb3344INCB3344: potent and selective small molecule CCR2 chemokine receptor antagonist
amd 070mavorixafor: a derivative of AMD3100; a CXCR4 blockeraminoquinoline
cenicriviroccenicriviroc : 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 3284INCB 3284: a CCR2 receptor antagonist
azd8309AZD8309: 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 acid3-(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
variabilinvariabilin: an RGD-containing antagonist of glycoprotein IIb-IIIa from the hard tick, Dermacentor variabilis; amino acid sequence given in first source