2026-05-21T23:03:19Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/151572024-09-27T09:22:29Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Menendez-Gutierrez, Maria Piedad author Porcuna, Jesus author Nayak, Ramesh C author Paredes, Ana author Niu, Haixia author Nunez, Vanessa author Paranjpe, Aditi author Gómez, MJ author Bhattacharjee, Anukana author Schnell, Daniel J author Sanchez-Cabo, Fatima author Welch JS author Salomonis, Nathan author Cancelas, JA author Ricote, Mercedes author 2022-11-08 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. Blood . 2022 Nov 8. 10.1182/blood.2022016832 1528-0020 Blood 36347014 http://hdl.handle.net/20.500.12105/15157 Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homeostasis.