Cell proliferation and CD11b expression are controlled independently during HL60 cell differentiation initiated by 1,25α-dihydroxyvitamin D3 or All-trans-retinoic acid
Cell proliferation and CD11b expression are controlled independently during HL60 cell differentiation initiated by 1,25α-dihydroxyvitamin D3 or All-trans-retinoic acid
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DOI：
10.1006/excr.2001.5200
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发表时间：
2001-05-15
影响因子：
3.7
通讯作者：
Brown, G
中科院分区：
文献类型：
--
作者：
Drayson, MT;Michell, RH;Brown, G
当1 α - 25-二羟基维生素D-3 （D-3）诱导HL60细胞分化为单核细胞时，在退出细胞周期和成熟完成之前，会出现大约三个缩短的细胞周期（“成熟分裂”）。在这里，我们发现在全反式维甲酸（ATRA）诱导的中性粒细胞分化过程中也发生了类似的成熟分裂，但没有缩短细胞周期。当细胞在G1早期通过“敏感窗口”时，ATRA和D-3都启动了这些成熟分裂。我们还研究了成熟分裂的开始和CD11b（一种早期表达的成熟标志物）的表达是否相关。用D-3或ATRA处理的细胞在完成第一次成熟分裂前9-14小时开始表达CD11b。用洗脱法从未同步的群体中分离出小的HL60细胞（几乎全部处于G1期）和大的细胞（G1期和S期）。当这些细胞与D-3或ATRA一起培养时，大多数细胞同步进入循环，繁殖和分化。在D-3处理后，富集G1的小细胞表达CD11b的速度略快于未同步培养或由晚期G1细胞和/或S期细胞主导的部分。d -3诱导的CD11b表达即使在胸苷嘧啶保持在G1/S边界的G1细胞中也以相似的速率发生。总之，单核细胞和中性粒细胞分化发生的细胞周期调控变化仅在G1早期触发，而CD11b的表达可以在细胞周期的大多数时间点启动。因此，分化剂必须通过至少部分独立的机制来调节分化的髓细胞的增殖和成熟。(C) 2001学术出版社。
When 1 alpha ,25-dihydroxyvitamin D-3 (D-3) induces HL60 cells to differentiate to monocytes, a burst of approximately three shortened cell cycles ("maturation divisions") precedes exit from cell cycle and completion of maturation. Here we show that similar maturation divisions occur during neutrophil differentiation induced by all-trans-retinoic acid (ATRA), but without shortening of the cell cycle. Both ATRA and D-3 initiate these maturation divisions as cells pass through a "window of sensitivity" during early G1. We also investigated whether the initiation of maturation divisions and of the expression of CD11b, an early-expressed maturation marker, are linked. Cells treated with D-3 or ATRA start to express CD11b after 9-14 h, before completing the first maturation division. Elutriation was used to isolate small HL60 cells (almost all in G1) and larger cells (in G1 and S phases) from unsynchronized populations. When these were cultured with D-3 or ATRA, most reentered cycle synchronously, multiplied, and differentiated. Following D-3 treatment, the G1-enriched small cells expressed CD11b slightly faster than unsynchronized cultures or fractions dominated by late G1 cells and/or S phase cells. D-3-induced CD11b expression occurred at a similar rate even in G1 cells that were held at the G1/S boundary by thymidine. In conclusion, changes in the control of the cell cycle that characterize the onset of monocytic and neutrophil differentiation are only triggered in early G1, but CD11b expression can be initiated from most points in the cell cycle. Differentiating agents must therefore regulate the proliferation and the maturation of differentiating myeloid cells by mechanisms that are at least partly independent. (C) 2001 Academic Press.