Metabolite Patterns in Human Myeloid Hematopoiesis Result from Lineage-Dependent Active Metabolic Pathways.
active metabolic pathways
hematopoietic stem cell differentiation
hematotoxicity
lineage commitment
metabolite patterns
metabolome screening
myeloid hematopoiesis
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
24 Aug 2020
24 Aug 2020
Historique:
received:
24
07
2020
revised:
18
08
2020
accepted:
21
08
2020
entrez:
28
8
2020
pubmed:
28
8
2020
medline:
2
3
2021
Statut:
epublish
Résumé
Assessment of hematotoxicity from environmental or xenobiotic compounds is of notable interest and is frequently assessed via the colony forming unit (CFU) assay. Identification of the mode of action of single compounds is of further interest, as this often enables transfer of results across different tissues and compounds. Metabolomics displays one promising approach for such identification, nevertheless, suitability with current protocols is restricted. Here, we combined a hematopoietic stem and progenitor cell (HSPC) expansion approach with distinct lineage differentiations, resulting in formation of erythrocytes, dendritic cells and neutrophils. We examined the unique combination of pathway activity in glycolysis, glutaminolysis, polyamine synthesis, fatty acid oxidation and synthesis, as well as glycerophospholipid and sphingolipid metabolism. We further assessed their interconnections and essentialness for each lineage formation. By this, we provide further insights into active metabolic pathways during the differentiation of HSPC into different lineages, enabling profound understanding of possible metabolic changes in each lineage caused by exogenous compounds.
Identifiants
pubmed: 32847028
pii: ijms21176092
doi: 10.3390/ijms21176092
pmc: PMC7504406
pii:
doi:
Substances chimiques
Antigens, CD34
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Federal Ministery of Science, Research and Art of Baden-Württemberg
ID : Scholarship for Lars Kaiser
Organisme : Steinbeis Center for Personalized Medicine
ID : StZ1789
Organisme : Deutsche Forschungsgemeinschaft
ID : CIBSS - EXC-2189 - Project ID 390939984
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