肝脏血小板生成素是维持骨髓造血干细胞所必需的。
Hepatic thrombopoietin is required for bone marrow hematopoietic stem cell maintenance.
作者信息
Decker Matthew, Leslie Juliana, Liu Qingxue, Ding Lei
机构信息
Columbia Stem Cell Initiative, Department of Rehabilitation and Regenerative Medicine, and Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
出版信息
Science. 2018 Apr 6;360(6384):106-110. doi: 10.1126/science.aap8861.
Hematopoietic stem cell (HSC) maintenance depends on extrinsic cues. Currently, only local signals arising from the bone marrow niche have been shown to maintain HSCs. However, it is not known whether systemic factors also sustain HSCs. We assessed the physiological source of thrombopoietin (TPO), a key cytokine required for maintaining HSCs. Using knock-in mice, we showed that TPO is expressed by hepatocytes but not by bone marrow cells. Deletion of from hematopoietic cells, osteoblasts, or bone marrow mesenchymal stromal cells does not affect HSC number or function. However, when is deleted from hepatocytes, bone marrow HSCs are depleted. Thus, a cross-organ factor, circulating TPO made in the liver by hepatocytes, is required for bone marrow HSC maintenance. Our results demonstrate that systemic factors, in addition to the local niche, are a critical extrinsic component for HSC maintenance.
造血干细胞（HSC）的维持依赖于外在信号。目前，仅有来自骨髓微环境的局部信号被证明可维持造血干细胞。然而，尚不清楚全身因素是否也能维持造血干细胞。我们评估了血小板生成素（TPO）的生理来源，TPO是维持造血干细胞所需的一种关键细胞因子。利用基因敲入小鼠，我们发现TPO由肝细胞表达，而非骨髓细胞表达。从造血细胞、成骨细胞或骨髓间充质基质细胞中删除TPO不会影响造血干细胞的数量或功能。然而，当从肝细胞中删除TPO时，骨髓造血干细胞会减少。因此，一种跨器官因子，即由肝细胞在肝脏中产生的循环TPO，是骨髓造血干细胞维持所必需的。我们的结果表明，除了局部微环境外，全身因素也是造血干细胞维持的关键外在组成部分。
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