Regulation of bone marrow hematopoietic stem cell is involved in high-altitude erythrocytosis
Regulation of bone marrow hematopoietic stem cell is involved in high-altitude erythrocytosis
复制标题
骨髓造血干细胞的调节参与高原红细胞增多症。
DOI：
10.1016/j.exphem.2010.10.006
复制
发表时间：
2011-01-01
影响因子：
2.6
通讯作者：
Gao, Yu-qi
中科院分区：
文献类型：
--
作者：
Li, Peng;Huang, Jian;Gao, Yu-qi
目的高原低氧可通过促红细胞生成素(EPO)引起红细胞生成增加。本研究观察了EPO反应不敏感的造血干细胞(HSC)对高原低氧环境的反应及对红细胞生成的影响。材料与方法利用模拟高原小鼠模型，观察不同EPO水平、不同氧气浓度、不同氧浓度、不同培养条件下正常LSK细胞的骨髓(BM)和脾系标志(-)、SCA1(+)、c-Kit(+)(LSK)的HSC。结果低氧小鼠骨髓和脾LSK细胞明显扩张，并伴随着增殖的增强，BM HSCs在高海拔地区的红细胞生成中可能比脾HSCs发挥更重要的作用。低氧小鼠的BM HSCs也发生了谱系命运的改变，表现为巨核红细胞前体细胞增多，粒细胞-巨噬细胞前体细胞周期性减少。低氧小鼠骨髓培养上清液(但不能升高EPO或不同的O-2张力)可诱导HSC群体的扩增和红系优先分化，这一现象部分是由于增加了IL-3和IL-6的分泌所致。结论本研究提出了一种新的高海拔红细胞增多症的HSC机制(C)2011 ISEH血液学与干细胞学会发表
Objective Hypoxia at high altitudes can lead to increased production of red blood cells through the hormone erythropoietin (EPO) In this study, we observed how the EPO-unresponsive hematopoietic stem cell (HSC) compartment responds to high altitude hypoxic environments and contributes to erythropoiesisMaterials and Methods Using a mouse model at simulated high altitude, the bone marrow (BM) and spleen lineage marker(-)Sca 1(+)c-Kit(+) (LSK) HSC compartment were observed in de tail Normal LSK cells were then cultured under different conditions (varying EPO levels, oxygen concentrations, and BM supernatants) to investigate the causes of the HSC responsesResults Hypoxic mice exhibited a marked expansion in BM and spleen LSK compartments, which were associated with enhanced proliferation BM HSCs seemed to play a more important role in erythropoiesis at high altitude than spleen HSCs There was also a lineage fate change of BM HSCs in hypoxic mice that was manifested in Increased megakaryocyte erythrocyte progenitors and periodically reduced granulocyte-macrophage progenitors in the BM The LSK cells in hypoxic mice displayed upregulated erythroid specific GATA 1 and downregulated granulocyte-macrophage specific PU 1 messenger RNA expression, as well as the capacity to differentiate into more erythroid precursors after culture BM culture supernatant from hypoxic mice (but not elevated EPO or varying O-2 tension) could induce expansion and erythroid-priority differentiation of the HSC population a phenomenon partially caused by increasing interleukin 3 and interleukin-6 secretion in the BMConclusions The present study suggests a new EPO-independent HSC mechanism of high-altitude erythrocytosis (C) 2011 ISEH Society for Hematology and Stem Cells Published by Elsevier Inc