当前位置: X-MOL 学术Science › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Hepatic thrombopoietin is required for bone marrow hematopoietic stem cell maintenance
Science ( IF 44.7 ) Pub Date : 2018-04-05 , DOI: 10.1126/science.aap8861
Matthew Decker 1 , Juliana Leslie 1 , Qingxue Liu 1 , Lei Ding 1
Affiliation  

Signaling hematopoietic stem cells from afar Throughout our entire life span, hematopoietic stem cells (HSCs) generate all of our blood cells. The bone marrow microenvironment, or niche, is key to activating stem cell activity. Decker et al. now show that thrombopoietin generated in the liver, but not from the local bone marrow niche, maintains HSCs in vivo in mice. Thus, systemic endocrine factors are needed to maintain somatic stem cells from a distance. These findings may be important when considering how to stimulate HSCs for therapeutic use. Science, this issue p. 106 Bone marrow hematopoietic stem cell maintenance relies on hepatic thrombopoietin. 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 TpoDsRed-CreER knock-in mice, we showed that TPO is expressed by hepatocytes but not by bone marrow cells. Deletion of Tpo from hematopoietic cells, osteoblasts, or bone marrow mesenchymal stromal cells does not affect HSC number or function. However, when Tpo 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.

中文翻译:

骨髓造血干细胞维持需要肝血小板生成素

从远处发送造血干细胞信号 在我们的整个生命周期中,造血干细胞 (HSC) 会产生我们所有的血细胞。骨髓微环境或生态位是激活干细胞活性的关键。德克尔等人。现在表明,在肝脏中产生的血小板生成素,而不是来自局部骨髓生态位,在小鼠体内维持 HSC。因此,需要全身内分泌因子来远距离维持体细胞干细胞。在考虑如何刺激 HSC 用于治疗时,这些发现可能很重要。科学,这个问题 p。106 骨髓造血干细胞的维持依赖于肝血小板生成素。造血干细胞 (HSC) 的维持取决于外在线索。目前,只有来自骨髓生态位的局部信号已被证明可以维持 HSC。然而,尚不清楚全身因素是否也维持 HSC。我们评估了血小板生成素 (TPO) 的生理来源,TPO 是维持 HSC 所需的关键细胞因子。使用 TpoDsRed-CreER 敲入小鼠,我们发现 TPO 由肝细胞表达,但不由骨髓细胞表达。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 HSC 的数量或功能。然而,当从肝细胞中删除 Tpo 时,骨髓 HSC 就会耗尽。因此,骨髓 HSC 维持需要一种跨器官因子,即由肝细胞在肝脏中产生的循环 TPO。我们的结果表明,除了局部生态位之外,系统性因素也是 HSC 维持的关键外在成分。维持 HSC 所需的关键细胞因子。使用 TpoDsRed-CreER 敲入小鼠,我们发现 TPO 由肝细胞表达,但不由骨髓细胞表达。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 HSC 的数量或功能。然而,当从肝细胞中删除 Tpo 时,骨髓 HSC 就会耗尽。因此,骨髓 HSC 维持需要一种跨器官因子,即由肝细胞在肝脏中产生的循环 TPO。我们的结果表明,除了局部生态位之外,系统性因素也是 HSC 维持的关键外在成分。维持 HSC 所需的关键细胞因子。使用 TpoDsRed-CreER 敲入小鼠,我们发现 TPO 由肝细胞表达,但不由骨髓细胞表达。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 HSC 的数量或功能。然而,当从肝细胞中删除 Tpo 时,骨髓 HSC 就会耗尽。因此,骨髓 HSC 维持需要一种跨器官因子,即由肝细胞在肝脏中产生的循环 TPO。我们的结果表明,除了局部生态位之外,系统性因素也是 HSC 维持的关键外在成分。或骨髓间充质基质细胞不影响 HSC 数量或功能。然而,当从肝细胞中删除 Tpo 时,骨髓 HSC 就会耗尽。因此,骨髓 HSC 维持需要一种跨器官因子,即由肝细胞在肝脏中产生的循环 TPO。我们的结果表明,除了局部生态位之外,系统性因素也是 HSC 维持的关键外在成分。或骨髓间充质基质细胞不影响 HSC 数量或功能。然而,当从肝细胞中删除 Tpo 时,骨髓 HSC 就会耗尽。因此,骨髓 HSC 维持需要一种跨器官因子,即由肝细胞在肝脏中产生的循环 TPO。我们的结果表明,除了局部生态位之外,系统性因素也是 HSC 维持的关键外在成分。
更新日期:2018-04-05
down
wechat
bug