Metabolic maturation of differentiating cardiosphere-derived cells.
Metabolic maturation of differentiating cardiosphere-derived cells.
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DOI：
10.1016/j.scr.2021.102422
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发表时间：
2021-07
影响因子：
1.2
通讯作者：
Carr CA
中科院分区：
文献类型：
--
作者：
Pakzad KK;Tan JJ;Anderson S;Board M;Clarke K;Carr CA
IV型胶原可促进心脏球源性细胞的增殖。纤维连接蛋白支持心脏球源性细胞的分化。随着心脏祖细胞的成熟，氧化代谢增加。刺激脂肪酸氧化促进心脏祖细胞成熟。心球来源的细胞(CDCs)可以在体外扩增，并被诱导沿着心脏谱系分化。为了概括成年心肌细胞的表型，分化的前体细胞需要上调线粒体葡萄糖和脂肪酸氧化。在这里，我们使用旨在维持茎干或促进分化的方案来培养和分化CDCs，包括使用过氧化物酶体增殖物激活受体α激动剂(PPARα)触发脂肪酸氧化。代谢变化的特点是在未分化的CDC和分化为心脏表型的过程中。大鼠心房CDC在纤维连接蛋白或IV型胶原上通过心球层的形成而扩增。用流式细胞仪和定量聚合酶链式反应检测细胞的分化，用放射性标记的底物定量测定细胞的底物代谢。IV型胶原促进CDCs的增殖，而纤维连接蛋白则促进细胞向心脏表型分化。在这两个群体中，5-氮胞苷治疗诱导了向氧化代谢的转变，表现为基因表达的变化，糖酵解通量减少，葡萄糖和棕榈酸的氧化增加。在分化过程中加入PPARα激动剂可增加葡萄糖和脂肪酸的氧化以及心脏基因的表达。我们的结论是，氧化代谢和细胞分化与其中一个的增加共同作用，推动另一个的增加。
Collagen IV promotes proliferation of cardiosphere-derived cells. Fibronectin supports differentiation of cardiosphere-derived cells. Oxidative metabolism increases as cardiac progenitors mature. Stimulating fatty acid oxidation promotes cardiac progenitor cell maturation. Cardiosphere-derived cells (CDCs) can be expanded in vitro and induced to differentiate along the cardiac lineage. To recapitulate the phenotype of an adult cardiomyocyte, differentiating progenitors need to upregulate mitochondrial glucose and fatty acid oxidation. Here we cultured and differentiated CDCs using protocols aimed to maintain stemness or to promote differentiation, including triggering fatty acid oxidation using an agonist of peroxisome proliferator-activated receptor alpha (PPARα). Metabolic changes were characterised in undifferentiated CDCs and during differentiation towards a cardiac phenotype. CDCs from rat atria were expanded on fibronectin or collagen IV via cardiosphere formation. Differentiation was assessed using flow cytometry and qPCR and substrate metabolism was quantified using radiolabelled substrates. Collagen IV promoted proliferation of CDCs whereas fibronectin primed cells for differentiation towards a cardiac phenotype. In both populations, treatment with 5-Azacytidine induced a switch towards oxidative metabolism, as shown by changes in gene expression, decreased glycolytic flux and increased oxidation of glucose and palmitate. Addition of a PPARα agonist during differentiation increased both glucose and fatty acid oxidation and expression of cardiac genes. We conclude that oxidative metabolism and cell differentiation act in partnership with increases in one driving an increase in the other.
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影响因子：
5
作者：
Chung S;Arrell DK;Faustino RS;Terzic A;Dzeja PP
通讯作者：
Dzeja PP
DOI：
10.1016/j.biocel.2017.05.007
发表时间：
2017-07
期刊：
The international journal of biochemistry & cell biology
影响因子：
--
作者：
Board M;Lopez C;van den Bos C;Callaghan R;Clarke K;Carr C
通讯作者：
Carr C
影响因子：
3.6
作者：
Malandraki-Miller S;Lopez CA;Al-Siddiqi H;Carr CA
通讯作者：
Carr CA
影响因子：
64.5
作者：
Ellison, Georgina M.;Vicinanza, Carla;Nadal-Ginard, Bernardo
通讯作者：
Nadal-Ginard, Bernardo
影响因子：
5.2
作者：
Hayashi, Yohei;Furue, Miho Kusuda;Asashima, Makoto
通讯作者：
Asashima, Makoto