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Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homesotasis

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE191163 | GEO | 2022/11/11

REPOSITORIES: GEO

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Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homeostasis

Project description:This SuperSeries is composed of the SubSeries listed below.

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Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homesotasis [Bulk]

Project description:Hematopoietic stem cells (HSCs) balance self-renewal and differentiation to maintain hematopoietic fitness throughout life. In steady-state conditions, HSC exhaustion is prevented by the maintenance of most HSCs in a quiescent state, with cells entering the cell cycle only occasionally. HSC quiescence is regulated by retinoid and fatty-acid ligands of transcriptional factors of the nuclear retinoid X receptor (RXR) family. Here, we show that dual deficiency for hematopoietic RXRa and RXRb induces HSC exhaustion, myeloid cell/megakaryocyte differentiation, and myeloproliferative-like disease. RXRa and RXRb maintain HSC quiescence, survival, and chromatin compaction; moreover, transcriptome changes in RXRa;RXRb-deficient HSCs include premature acquisition of an aging-like HSC signature, MYC pathway upregulation, and RNA intron retention. Fitness loss and associated RNA transcriptome and splicing alterations in RXRa;RXRb-deficient HSCs are prevented by Myc haploinsufficiency. Our study reveals the critical importance of RXRs for the maintenance of HSC fitness and their protection from premature aging.

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Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homesotasis [Single Cells]

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Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homesotasis

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Project description:Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homesotasis [Bulk]

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Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence by repressing MYC pathway activation [RXR_CnR]

Project description:Hematopoietic stem cells (HSCs) maintain homeostasis and fitness by balancing self-renewal and differentiation. Alterations to the symmetry of HSC divisions reduce quiescence and induce myeloid/megakaryocyte-biased hematopoiesis. Here, we show that HSC self-renewal, fitness, and function are preserved by the master transcription factor retinoid X receptor (RXR). We demonstrate that dual lack of hematopoietic RXRα and RXRβ induces HSC asymmetric cell division resulting in HSC exhaustion and age-associated myeloproliferative disease. Characterization of transcriptomic and epigenetic changes in RXR-deficient HSCs demonstrated chromatin opening, acquisition of a premature aging-like HSC signature, MYC pathway upregulation, and RNA intron retention. Myc haploinsufficiency completely prevents the loss of RXR-deficient HSC activity. Our study unveils the critical relevance of RXR for HSC homeostasis and fitness.

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Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence by repressing MYC pathway activation [HISTONE_CnR]

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Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence by repressing MYC pathway activation [RXR_ATACSeq]

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