An aged bone marrow niche restrains rejuvenated hematopoietic stem cells,STEM CELLS

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An aged bone marrow niche restrains rejuvenated hematopoietic stem cells
STEM CELLS ( IF 4.0 ) Pub Date : 2021-04-13 , DOI: 10.1002/stem.3372
Novella Guidi ₁ , Gina Marka ₁ , Vadim Sakk ₁ , Yi Zheng ₂ , Maria Carolina Florian ₁ , Hartmut Geiger ₁

Affiliation

Aging-associated leukemia and aging-associated immune remodeling are in part caused by aging of hematopoietic stem cells (HSCs). An increase in the activity of the small RhoGTPase cell division control protein 42 (Cdc42) within HSCs causes aging of HSCs. Old HSCs, treated ex vivo with a specific inhibitor of Cdc42 activity termed CASIN, stay rejuvenated upon transplantation into young recipients. We determined in this study the influence of an aged niche on the function of ex vivo rejuvenated old HSCs, as the relative contribution of HSCs intrinsic mechanisms vs extrinsic mechanisms (niche) for aging of HSCs still remain unknown. Our results show that an aged niche restrains the function of ex vivo rejuvenated HSCs, which is at least in part linked to a low level of the cytokine osteopontin found in aged niches. The data imply that sustainable rejuvenation of the function of aged HSCs in vivo will need to address the influence of an aged niche on rejuvenated HSCs.

中文翻译：

老化的骨髓生态位抑制再生的造血干细胞

与衰老相关的白血病和与衰老相关的免疫重塑部分是由造血干细胞 (HSC) 的衰老引起的。HSC 内小 RhoGTPase 细胞分裂控制蛋白 42 (Cdc42) 活性的增加导致 HSC 老化。旧的 HSCs，用一种称为 CASIN 的 Cdc42 活性特异性抑制剂进行离体治疗，在移植到年轻受体后保持活力。我们在这项研究中确定了老化的生态位对离体再生的旧 HSC 功能的影响，因为 HSC 内在机制与外在机制（生态位）对 HSC 老化的相对贡献仍然未知。我们的研究结果表明，老年生态位抑制了离体再生 HSC 的功能，这至少部分与老年生态位中发现的低水平的细胞因子骨桥蛋白有关。

更新日期：2021-04-13

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