Kruppel-like factor 15 induces the development of mature hepatocyte-like cells from hepatoblasts.
Kruppel-like factor 15 induces the development of mature hepatocyte-like cells from hepatoblasts.
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DOI：
10.1038/s41598-021-97937-6
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发表时间：
2021-09-17
影响因子：
4.6
通讯作者：
Kamiya A
中科院分区：
文献类型：
--
作者：
Anzai K;Tsuruya K;Ida K;Kagawa T;Inagaki Y;Kamiya A
肝脏是控制体内稳态的重要代谢器官。而且，它具有造血器官的功能，但在发育过程中其代谢功能较低。肝细胞是肝脏的实质细胞，在胎儿期通过肝祖细胞的成熟而获得各种代谢功能。然而，这种分子机制仍不清楚。本研究通过对小鼠胎儿和成年肝细胞中转录调节因子的表达进行综合分析，确定Kruppel样因子15（KLF15）是一种新的肝成熟调节因子。 KLF15是一种转录因子，其在肝脏中的表达从胚胎阶段到整个发育过程不断增加。 KLF15 诱导小鼠胚胎肝细胞中肝功能基因的过度表达。此外，我们发现KLF15的表达还可以诱导源自人诱导多能干细胞（iPSC）的成肝细胞中肝功能基因的表达。此外，KLF15还增加了肝功能基因酪氨酸转氨酶的启动子活性。 KLF15 还抑制成肝细胞的增殖。这些结果表明KLF15通过靶基因的转录激活和细胞周期控制来诱导肝成熟。
The liver is an important metabolic organ that controls homeostasis in the body. Moreover, it functions as a hematopoietic organ, while its metabolic function is low during development. Hepatocytes, which are parenchymal cells of the liver, acquire various metabolic functions by the maturation of hepatic progenitor cells during the fetal period; however, this molecular mechanism is still unclear. In this study, Kruppel-like factor 15 (KLF15) was identified as a new regulator of hepatic maturation through a comprehensive analysis of the expression of transcriptional regulators in mouse fetal and adult hepatocytes. KLF15 is a transcription factor whose expression in the liver increases from the embryonic stage throughout the developmental process. KLF15 induced the overexpression of liver function genes in mouse embryonic hepatocytes. Furthermore, we found that the expression of KLF15 could also induce the expression of liver function genes in hepatoblasts derived from human induced pluripotent stem cells (iPSCs). Moreover, KLF15 increased the promoter activity of tyrosine aminotransferase, a liver function gene. KLF15 also suppressed the proliferation of hepatoblasts. These results suggest that KLF15 induces hepatic maturation through the transcriptional activation of target genes and cell cycle control.
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影响因子：
3.7
作者：
Yanagida A;Ito K;Chikada H;Nakauchi H;Kamiya A
通讯作者：
Kamiya A
影响因子：
5.3
作者：
Hayhurst, GP;Lee, YH;Gonzalez, FJ
通讯作者：
Gonzalez, FJ
影响因子：
1.2
作者：
Kamiya, Akihide;Chikada, Hiromi;Inagaki, Yutaka
通讯作者：
Inagaki, Yutaka
影响因子：
4.6
作者：
Suzuki, A;Iwama, A;Taniguchi, H
通讯作者：
Taniguchi, H
影响因子：
4.7
作者：
Suzuki, A;Obi, K;Mochizuki, H
通讯作者：
Mochizuki, H