Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/15157
Título
Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homeostasis.
Autor(es)
Menendez-Gutierrez, Maria Piedad CNIC | Porcuna, Jesus CNIC | Nayak, Ramesh C | Paredes, Ana | Niu, Haixia | Nunez, Vanessa CNIC | Paranjpe, Aditi | Gómez, MJ | Bhattacharjee, Anukana | Schnell, Daniel J | Sanchez-Cabo, Fatima CNIC | Welch JS | Salomonis, Nathan | Cancelas, JA | Ricote, Mercedes CNIC
Fecha de publicación
2022-11-08
Cita
Blood . 2022 Nov 8.
Idioma
Inglés
Tipo de documento
journal article
Resumen
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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DOI
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