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Omics · study · 2026

RACK1 maintains mouse hematopoietic stem cells by directly binding to and stabilizing LDB1

Listed in NCBI GEO

Hematopoietic stem cells (HSCs), with the capability of self-renewal and all blood lineages reconstruction, serve a crucial role in maintaining steady-state hematopoiesis within bone marrow during adulthood.

Description

The adaptor protein receptor for activated C kinase 1 (RACK1) has been implicated in the regulation of various transcription factors and signaling pathways by modulating their activation and/or stability. However, the specific role of RACK1 in the transcriptional control of HSC fates has not been previously elucidated.

Here, we reported that RACK1 is enriched in adult mouse hematopoietic progenitors. Adulthood Rack1 deletion in IFN-I-responsive cells leads to rapid and profound hematopoietic failure and HSC loss. Furthermore, prenatal deletion of Rack1 in hematopoietic cells results in reduced and defective HSCs in the fetal liver.

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Such phenotypes result from cell-intrinsic defects with enhanced apoptosis of HSCs. Single-cell RNA sequencing indicates that adulthood Rack1 deletion in IFN-I-responsive cells leads to aberrant lineage-geneset-scores of transcriptional HSCs and the emergence of HSC-like cells. Mechanistically, RACK1 prevents HSC loss through maintaining the protein level of LDB1.

The direct interaction between RACK1 and LDB1 stabilizes LDB1 through suppressing its ubiquitination and subsequent degradation.

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Life Sciences
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RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 75%
Provenance · 1 source records, 10 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE31510815 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[modality].local:modality:single-cell-rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title