Kruppel-like factor 15 induces the development of mature hepatocyte-like cells from hepatoblasts

Abstract 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 maturat...

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Autores principales: Kazuya Anzai, Kota Tsuruya, Kinuyo Ida, Tatehiro Kagawa, Yutaka Inagaki, Akihide Kamiya
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:ba896f6abdb640a7b6c98832be2442292021-12-02T17:25:33ZKruppel-like factor 15 induces the development of mature hepatocyte-like cells from hepatoblasts10.1038/s41598-021-97937-62045-2322https://doaj.org/article/ba896f6abdb640a7b6c98832be2442292021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97937-6https://doaj.org/toc/2045-2322Abstract 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.Kazuya AnzaiKota TsuruyaKinuyo IdaTatehiro KagawaYutaka InagakiAkihide KamiyaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Kazuya Anzai
Kota Tsuruya
Kinuyo Ida
Tatehiro Kagawa
Yutaka Inagaki
Akihide Kamiya
Kruppel-like factor 15 induces the development of mature hepatocyte-like cells from hepatoblasts
description Abstract 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.
format article
author Kazuya Anzai
Kota Tsuruya
Kinuyo Ida
Tatehiro Kagawa
Yutaka Inagaki
Akihide Kamiya
author_facet Kazuya Anzai
Kota Tsuruya
Kinuyo Ida
Tatehiro Kagawa
Yutaka Inagaki
Akihide Kamiya
author_sort Kazuya Anzai
title Kruppel-like factor 15 induces the development of mature hepatocyte-like cells from hepatoblasts
title_short Kruppel-like factor 15 induces the development of mature hepatocyte-like cells from hepatoblasts
title_full Kruppel-like factor 15 induces the development of mature hepatocyte-like cells from hepatoblasts
title_fullStr Kruppel-like factor 15 induces the development of mature hepatocyte-like cells from hepatoblasts
title_full_unstemmed Kruppel-like factor 15 induces the development of mature hepatocyte-like cells from hepatoblasts
title_sort kruppel-like factor 15 induces the development of mature hepatocyte-like cells from hepatoblasts
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/ba896f6abdb640a7b6c98832be244229
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