Role of cell-extrinsic HO-1 in aging of hematopoietic stem cells

We investigated how lack of HO-1 affects function and aging of hematopoietic stem cells (HSCs). We analyzed transcriptome of young and old HSCs from HO-1 KO mice and compared them to young and old WT HSC, and HSC from WT mice that were bled. We also profiled transcriptome of endothelial cells and mesenchymal cells from bone marrow from HO-1 KO mice. Using genetic and functional assays we showed that heme oxygenase-1 deficiency triggers premature exhaustion of hematopoietic stem cells in cell-extrinsic manner.

本研究旨在探讨血红素氧合酶-1（heme oxygenase-1, HO-1）缺失对造血干细胞（hematopoietic stem cells, HSCs）的功能与衰老的影响。我们对来自HO-1基因敲除（knockout, KO）小鼠的年轻与年老造血干细胞进行了转录组分析，并将结果与野生型（wild type, WT）年轻、年老造血干细胞，以及经采血处理的野生型小鼠造血干细胞的转录组数据进行了对比。此外，我们还对HO-1基因敲除小鼠骨髓来源的内皮细胞与间充质细胞开展了转录组分析。通过遗传与功能实验，我们证实血红素氧合酶-1缺失可通过细胞外源性方式触发造血干细胞的过早耗竭。