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MAEA is an E3 ubiquitin ligase promoting autophagy and maintenance of haematopoietic stem cells

UID: 10633

Author(s): Wei, Qiaozhi, Frenette, Paul S.

Description
Summary from the GEO: "Haematopoietic stem cells (HSCs) tightly regulate their quiescence, proliferation, and differentiation to generate blood cells during the entire lifetime. The mechanisms by which these critical activities are balanced are still unclear. Here, we report that Macrophage-Erythroblast Attacher (MAEA, also known as EMP), a receptor thus far only identified in erythroblastic island1, is a membrane-associated E3 ubiquitin ligase essential for HSC maintenance and lymphoid commitment. Maea is highly expressed in HSCs and its deletion in mice severely impairs HSC quiescence and function and leads to a lethal myeloproliferative syndrome. By contrast, MAEA expression is essential for the development of acute myeloid leukaemia (AML) and up-regulated in human and mouse AML. Mechanistically, we have found that the surface expression of several haematopoietic cytokine receptors (e.g. MPL, FLT3) is stabilised in absence of Maea, thereby prolonging their intracellular signalling. Additionally, the autophagy flux in HSCs, but not in mature haematopoietic cells, is dramatically impaired. Administration of autophagy-inducing compounds rescues the functional defects of Maea-deficient HSCs. These results thus suggest that MAEA is a pivotal E3 ubiquitin ligase guarding HSC function via autophagy."

Overall design from the GEO: "mRNA profiles were generated from bone marrow hematopoietic stem cells of 8wk old control and MaeaCsf1r-Cre littermates in triplicates by Illumina NextSeq500 sequencing"
Subject of Study
Mus musculus
Subject(s)
Cell Adhesion Molecules
Cytoskeletal Proteins
Gene Expression Profiling
Hematopoiesis
Hematopoietic Stem Cells
Leukemia, Myeloid, Acute
Lymphokines
Ubiquitin-Protein Ligases
OncoTree Cancer Type(s)
Acute Myeloid Leukemia
Access via GEO

Plain Text Data of expression profiling by high throughput sequencing
Accession #: GSE133431

Access via SRA

RNA Sequence reads for 6 samples
Accession #: SRP212200

Access via BioProject

Additional information about overall initiative.
Accession #: PRJNA551452

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus, SRA, and BioProject databases provide open access to these files.
Associated Publications
Wei Q, Pinho S, Dong S, et al. MAEA is an E3 ubiquitin ligase promoting autophagy and maintenance of haematopoietic stem cells. Nature Communications. 2021; 12:2522.
Data Type
Genomic
Equipment Used
Illumina NextSeq 500
Software Used
SRA Toolkit

The NCBI SRA Toolkit enables reading ("dumping") of sequencing files from the SRA database and writing ("loading") files into the .sra format.

Dataset Format(s)
Plain Text
Data Tool(s)
RNA Seq
Dataset Size
604 KB (TXT), 20.7 GB (SRA)
Data Catalog Record Updated
2023-12-07