Rolls Asya, Pang Wendy W, Ibarra Ingrid, Colas Damien, Bonnavion Patricia, Korin Ben, Heller H Craig, Weissman Irving L, de Lecea Luis
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, USA.
Rappaport Medical School, Technion, Israel Institute of Technology, Haifa 31096, Israel.
Nat Commun. 2015 Oct 14;6:8516. doi: 10.1038/ncomms9516.
Many of the factors affecting the success of haematopoietic cell transplantation are still unknown. Here we show in mice that donor sleep deprivation reduces the ability of its haematopoietic stem cells (HSCs) to engraft and reconstitute the blood and bone marrow of an irradiated recipient by more than 50%. We demonstrate that sleep deprivation downregulates the expression of microRNA (miR)-19b, a negative regulator of the suppressor of cytokine signalling (SOCS) genes, which inhibit HSC migration and homing. Accordingly, HSCs from sleep-deprived mice have higher levels of SOCS genes expression, lower migration capacity in vitro and reduced homing to the bone marrow in vivo. Recovery of sleep after sleep deprivation restored the reconstitution potential of the HSCs. Taken together, this study provides insights into cellular and molecular mechanisms underlying the effects of sleep deprivation on HSCs, emphasizing the potentially critical role of donor sleep in the success of bone marrow transplantation.
许多影响造血细胞移植成功的因素仍不明确。我们在小鼠中发现,供体睡眠剥夺会使其造血干细胞(HSC)植入并重建受辐照受体的血液和骨髓的能力降低50%以上。我们证明,睡眠剥夺会下调微小RNA(miR)-19b的表达,miR-19b是细胞因子信号抑制因子(SOCS)基因的负调节因子,而SOCS基因会抑制HSC迁移和归巢。因此,来自睡眠剥夺小鼠的HSC具有更高水平的SOCS基因表达、更低的体外迁移能力以及在体内向骨髓归巢的能力降低。睡眠剥夺后的睡眠恢复恢复了HSC的重建潜力。综上所述,本研究深入探讨了睡眠剥夺对HSC影响的细胞和分子机制,强调了供体睡眠在骨髓移植成功中的潜在关键作用。