Lipoprotein lipase regulates hematopoietic stem progenitor cell maintenance through DHA supply.
Lipoprotein lipase regulates hematopoietic stem progenitor cell maintenance through DHA supply.
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DOI：
10.1038/s41467-018-03775-y
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发表时间：
2018-04-03
影响因子：
16.6
通讯作者：
Miller YI
中科院分区：
文献类型：
--
作者：
Liu C;Han T;Stachura DL;Wang H;Vaisman BL;Kim J;Klemke RL;Remaley AT;Rana TM;Traver D;Miller YI
脂蛋白脂肪酶（LPL）介导甘油三酯（tg）的水解，为组织提供游离脂肪酸（FFAs）。在这里，我们发现LPL活性对于造血干细胞（HSPC）的维持也是必需的。在斑马鱼的最终造血过程中，敲除Lpl或其必需的辅助因子Apoc2可显著降低HSPC的扩增。人类APOC2模拟肽或携带APOC2的人类极低密度脂蛋白可以挽救APOC2的表型，但在lpl突变的斑马鱼中却没有。创造异种的apoc2和lpl突变斑马鱼可以拯救两者的造血缺陷。二十二碳六烯酸（DHA）被认为是HSPC扩张的重要因素。FFA-DHA，而不是TG-DHA，可以修复apo2和lpl突变斑马鱼的HSPC缺陷。在断奶时，Apoc2突变小鼠也观察到血细胞计数减少。这些结果表明，lpl介导的必需脂肪酸DHA的释放调节HSPC的扩增和最终造血。脂蛋白脂肪酶（LPL）水解甘油三酯，为肌肉提供游离脂肪酸（FFAs）作为能量，为脂肪细胞提供储存。在这里，作者证明了Lpl及其产物，游离脂肪酸二十二碳六烯酸（DHA）是斑马鱼胚胎发生期间造血干细胞祖细胞扩增所必需的。
Lipoprotein lipase (LPL) mediates hydrolysis of triglycerides (TGs) to supply free fatty acids (FFAs) to tissues. Here, we show that LPL activity is also required for hematopoietic stem progenitor cell (HSPC) maintenance. Knockout of Lpl or its obligatory cofactor Apoc2 results in significantly reduced HSPC expansion during definitive hematopoiesis in zebrafish. A human APOC2 mimetic peptide or the human very low-density lipoprotein, which carries APOC2, rescues the phenotype in apoc2 but not in lpl mutant zebrafish. Creating parabiotic apoc2 and lpl mutant zebrafish rescues the hematopoietic defect in both. Docosahexaenoic acid (DHA) is identified as an important factor in HSPC expansion. FFA-DHA, but not TG-DHA, rescues the HSPC defects in apoc2 and lpl mutant zebrafish. Reduced blood cell counts are also observed in Apoc2 mutant mice at the time of weaning. These results indicate that LPL-mediated release of the essential fatty acid DHA regulates HSPC expansion and definitive hematopoiesis. Lipoprotein lipase (LPL) hydrolyzes triglycerides to supply free fatty acids (FFAs) to muscle for energy and adipocytes for storage. Here, the authors demonstrate that Lpl and its product, the FFA docosahexaenoic acid (DHA) are required for haematopoietic stem progenitor cell expansion during zebrafish embryogenesis.
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影响因子：
4.4
作者：
de Vogel-van den Bosch HM;Bünger M;de Groot PJ;Bosch-Vermeulen H;Hooiveld GJ;Müller M
通讯作者：
Müller M
影响因子：
3.7
作者：
Lalonde S;Stone OA;Lessard S;Lavertu A;Desjardins J;Beaudoin M;Rivas M;Stainier DYR;Lettre G
通讯作者：
Lettre G
影响因子：
4.4
作者：
Davies BS;Beigneux AP;Fong LG;Young SG
通讯作者：
Young SG
影响因子：
4.3
作者：
Dhenge, Ankita;Limbkar, Kedar;Limaye, Lalita
通讯作者：
Limaye, Lalita
DOI：
10.1073/pnas.1308335110
发表时间：
2013-08-20
影响因子：
11.1
作者：
Jao, Li-En;Wente, Susan R.;Chen, Wenbiao
通讯作者：
Chen, Wenbiao