Metabolomics

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GNPS Understanding the metabolic regulation of murine hematopoietic emergence


ABSTRACT: In vertebrates, lifelong supply of all the blood cell types in suitable numbers is maintained by the hematopoietic stem cells (HSCs). During development, these HSCs emerge in the aorta-gonad-mesonephros (AGM) from specialized vascular endothelium through a transdifferentiation process, called as endothelial-to-hematopoietic transition (EHT). During this process, select endothelial cells (CD31+c-kit- or CD31PCKITN) switch to a hematopoietic transcriptional program, undergo morphological changes and become hemogenic (CD31+c-kit+ or CD31PCKITP) and gives rise to hematopoietic cells (CD31-c-kit+ or CD31NCKITP). A complex interplay of key transcription factors and signaling pathways coordinates the whole process. Specific metabolic signature of a cell can precisely define its phenotype. Evidence has emerged that cellular phenotype and function can be driven according to the changes in cellular metabolism. Metabolic programs, which are stage specific, allow stem cells to adapt their function in different microenvironments. In the present study, we performed nano LC-MS/MS based proteomic analysis to understand the molecular program involved in the transdifferentiation of endothelial to hematopoietic cells.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Dr. Satish Khurana  

PROVIDER: MSV000092085 | GNPS | Fri Jun 02 03:28:00 BST 2023

SECONDARY ACCESSION(S): PXD042649

REPOSITORIES: GNPS

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Publications

Glycolytic state of aortic endothelium favors hematopoietic transition during the emergence of definitive hematopoiesis.

Pv Anu A   Mehatre Shubham Haribhau SH   Verfaillie Catherine M CM   Alam Mohammad Tauqeer MT   Khurana Satish S  

Science advances 20240216 7


The first definitive hematopoietic progenitors emerge through the process of endothelial-to-hematopoietic transition in vertebrate embryos. With molecular regulators for this process worked out, the role of metabolic pathways used remains unclear. Here, we performed nano-LC-MS/MS-based proteomic analysis and predicted a metabolic switch from a glycolytic to oxidative state upon hematopoietic transition. Mitochondrial activity, glucose uptake, and glycolytic flux analysis supported this hypothesi  ...[more]

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