Nicotinamide (vitamin B3) increases the polyploidisation and proplatelet formation of cultured primary human megakaryocytes
Nicotinamide (vitamin B3) increases the polyploidisation and proplatelet formation of cultured primary human megakaryocytes
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DOI：
10.1111/j.1365-2141.2006.06341.x
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发表时间：
2006-11-01
影响因子：
6.5
通讯作者：
Miller, William M.
中科院分区：
文献类型：
--
作者：
Giammona, Lisa M.;Fuhrken, Peter G.;Miller, William M.
巨核细胞（Mk）的成熟涉及多倍体化，产生的血小板数量随着Mk DNA含量的增加而增加。培养的人MK细胞的倍性水平远低于体内观察到的水平。这项研究表明，将水溶性维生素烟酰胺（NIC）添加到与血小板生成素（Tpo）一起培养的动员的外周血CD 34（+）细胞中，使高倍性（>= 8 N）MK细胞的百分比增加一倍以上。无论Mk分化的供体依赖性差异如何，都观察到了这一点。此外，NIC培养物中的MK细胞更大，具有更高的分叶核，达到64 N的最大DNA含量（与单独使用Tpo的16 N相比），并表现出更频繁和更精细的细胞质延伸。NIC还增加了培养的原代鼠MK细胞和MK分化的细胞系模型（CHRF-288）的倍性。然而，NIC并没有改变Mk承诺，细胞凋亡，或在开始的时间内有丝分裂。尽管观察到NIC添加的显着的表型差异，基因表达微阵列分析显示，在有或没有NIC的原代人Mk文化相似的整体转录模式，表明NIC没有破坏正常的Mk转录程序。阐明NIC增加Mk成熟的机制可能会导致Mk和血小板疾病治疗的进展。
Megakaryocytic (Mk) cell maturation involves polyploidisation, and the number of platelets produced increases with Mk DNA content. Ploidy levels in cultured human MK cells are much lower than those observed in vivo. This study demonstrated that adding the water-soluble vitamin nicotinamide (NIC) to mobilised peripheral blood CD34(+) cells cultured with thrombopoietin (Tpo) more than doubled the percentage of high-ploidy (>= 8N) MK cells. This was observed regardless of donor-dependent differences in Mk differentiation. Furthermore, MK cells in cultures with NIC were larger, had more highly lobated nuclei, reached a maximum DNA content of 64N (vs. 16N with Tpo alone), and exhibited more frequent and more elaborate cytoplasmic extensions. NIC also increased the ploidy of cultured primary murine MK cells and a cell line model (CHRF-288) of Mk differentiation. However, NIC did not alter Mk commitment, apoptosis, or the time at which endomitosis was initiated. Despite the dramatic phenotypic differences observed with NIC addition, gene expression microarray analysis revealed similar overall transcriptional patterns in primary human Mk cultures with or without NIC, indicating that NIC did not disrupt the normal Mk transcriptional program. Elucidating the mechanisms by which NIC increases Mk maturation could lead to advances in the treatment of Mk and platelet disorders.