Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene expression analysis of Kasumi9 cells cultured with or without BCAA

ABSTRACT: The branched-chain amino acid (BCAA) metabolism plays pleiotropic roles in homeostasis. Here we show that human acute leukemia-initiating cells (LICs), but not normal hematopoietic stem cells, are heavily addicted to the BCAA metabolism, irrespective of myeloid or lymphoid types. To clarify how BCAA metabolism affect the gene expression of human acute leukemia cells, we examined the gene expression alteration in human acute leukemia cell lines in control and BCAA-resrticted culture conditions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE131814 | GEO | 2019/07/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Gene expression analysis of Jurkat cells cultured with or without BCAA

2019-07-01 | GSE131815 | GEO

Gene expression analysis of THP-1 cells cultured with or without BCAA

2019-07-01 | GSE131813 | GEO

Genome-wide maps of H3K27me3 chromatin modification status regulated by branched chain amino acids (BCAA) metabolism in human acute leukemia

Project description:The branched-chain amino acid (BCAA) metabolism plays pleiotropic roles in homeostasis. Here we show that human acute leukemia-initiating cells (LICs), but not normal hematopoietic stem cells, are heavily addicted to the BCAA metabolism, irrespective of myeloid or lymphoid types. Human acute leukemia cells had a high level of BCAAs, transporting free BCAAs into the cytoplasm. Functional inhibition of BCAA transaminase-1 (BCAT1), a catalytic enzyme for BCAAs, induced apoptosis of human LICs, and suppressed reconstitution of human leukemia in xenograft models. Furthermore, deprivation of BCAAs from daily diet in mice transplanted with human LICs strongly inhibited their expansion and self-renewal in vivo. The BCAT1 inhibition inactivates the PRC2 function for epigenetic maintenance of stem cell signatures via downregulation of EZH2 and EED, critical PRC2 components, and inhibited the mTORC1 signaling for leukemia propagation. Thus, targeting the BCAA metabolism should be a powerful approach to erase cancer stemness in human acute leukemias.

2019-08-01 | GSE132512 | GEO

Gene expression alteration regulated by BCAA-metabolism in human acute leukemia

Project description:Gene expression alteration regulated by BCAA-metabolism in human acute leukemia

| PRJNA545241 | ENA

Whole exome sequencing analysis of bone marrow c-Kit+ leukemia cells in Nras-G12D with Ezh2 KO (E2-KO) mice

Project description:Epigenetic gene regulation and metabolism are highly intertwined, yet little is known whether and how altered epigenetics influences cellular metabolism in cancer progression. Here we show that EZH2 and NRasG12D mutations cooperatively induce progression of myeloproliferative neoplasms to fully penetrant, transplantable and lethal myeloid leukemias in mouse. EZH1, an EZH2 homolog, is indispensable for EZH2-deficient leukemia-initiating cells (LICs) and constitutes an epigenetic vulnerability. BCAT1, the first enzyme catalyzing transamination of branched-chain amino acids (BCAAs), is repressed by EZH2 in normal hematopoiesis and aberrantly activated in EZH2-deficient myeloid neoplasms in mouse and human. Enhanced BCAT1 promotes BCAA production in LICs ex vivo and in vivo, resulting in activated mTOR signaling. Genetic and pharmacological inhibition of BCAT1 selectively impairs EZH2-deficient LICs and constitutes a metabolic vulnerability. These findings establish an example how epigenetic alterations modify metabolic adaptation in myeloid transformation and provide a rationale for targeting the epigenetic and metabolic liabilities of cancer-initiating cells.

2019-09-01 | GSE122585 | GEO

RNA-seq analysis of transcriptomic changes in bone marrow LSK cells in WT, G12D, Ezh2-KO and G12D with Ezh2-KO (G12D_Ezh2-KO) mice [RNA-seq]

2019-06-17 | GSE132079 | GEO

ChIP-seq analysis of H3K4me3,H3K27ac and H3K27me3 in bone marrow LSK cells in WT, G12D, Ezh2-KO and G12D with Ezh2-KO (G12D_Ezh2-KO) mice

2019-06-17 | GSE132078 | GEO

ATAC-seq analysis in bone marrow LSK cells in WT, G12D, Ezh2-KO and G12D with Ezh2-KO (G12D_Ezh2-KO) mice

2019-06-17 | GSE132077 | GEO

Genome-wide maps of H3K27me3 chromatin modification status regulated by branched chain amino acids (BCAA) metabolism in human acute leukemia

Project description:Genome-wide maps of H3K27me3 chromatin modification status regulated by branched chain amino acids (BCAA) metabolism in human acute leukemia

| PRJNA548258 | ENA

The BCKDH kinase and phosphatase integrate BCAA and lipid metabolism via regulation of ATP-citrate lyase

Project description:Strong associations exist between branched chain amino acids (BCAA) and dysregulated glucose and lipid metabolism, but the underlying mechanisms are not well understood. Here we report that inhibition of the kinase (BDK) or overexpression of the phosphatase (PPM1K) that regulate branched-chain ketoacid dehydrogenase (BCKDH), the committed step of BCAA catabolism, lowers circulating BCAA, reduces hepatic steatosis and improves glucose tolerance in the absence of weight loss in Zucker fatty rats. Phosphoproteomics analysis identified ATP-citrate lyase (ACL) as an alternate substrate of BDK and PPM1K. Overexpression of BDK in liver of lean rats increased ACL phosphorylation and activated de novo lipogenesis. Moreover, BDK and PPM1K transcript levels were increased and repressed, respectively, in response to fructose feeding and expression of the ChREBP transcription factor. These studies identify BDK and PPM1K as a regulatory node that integrates BCAA, glucose, and lipid metabolism via reciprocal regulation of BCKDH and ACL. Modulation of this node relieves key disease phenotypes in a genetic model of severe obesity and metabolic dysfunction.

2018-05-18 | PXD009122 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data