Alternative Titleトランスクリプトーム解析が示す肝細胞不均一性 : 倍数性、肝内分布、幹/前駆細胞の観点から
Note (General)By using rat hepatocytes with different ploidy statuses, a bulk transcriptome and single-cell quantitative reverse-transcription polymerase chain reaction show that diploid hepatocytes are preferentially located in the pericentral region. Single-cell analysis further identifies a subpopulation within the 2c hepatocytes that co-express the mature hepatocyte markers and liver progenitor cell markers. BACKGROUND & AIMS: There is a long-standing debate regarding the biological significance of polyploidy in hepatocytes. Recent studies have provided increasing evidence that hepatocytes with different ploidy statuses behave differently in a context-dependent manner (eg, susceptibility to oncogenesis, regenerative ability after injury, and in vitro proliferative capacity). However, their overall transcriptomic differences in a physiological context is not known. METHODS: By using microarray transcriptome analysis, we investigated the heterogeneity of hepatocyte populations with different ploidy statuses. Moreover, by using single-cell quantitative reverse-transcription polymerase chain reaction (scPCR) analysis, we investigated the intrapopulational transcriptome heterogeneity of 2c and 4c hepatocytes. RESULTS: Microarray analysis showed that cell cycle–related genes were enriched in 8c hepatocytes, which is in line with the established notion that polyploidy is formed via cell division failure. Surprisingly, in contrast to the general consensus that 2c hepatocytes reside in the periportal region, in our bulk transcriptome and scPCR analyses, the 2c hepatocytes consistently showed pericentral hepatocyte-enriched characteristics. In addition, scPCR analysis identified a subpopulation within the 2c hepatocytes that co-express the liver progenitor cell markers Axin2, Prom1, and Lgr5, implying the potential biological relevance of this subpopulation. CONCLUSIONS: This study provides new insights into hepatocyte heterogeneity, namely 2c hepatocytes are preferentially localized to the pericentral region, and a subpopulation of 2c hepatocytes show liver progenitor cell–like features in terms of liver progenitor cell marker expression (Axin2, Prom1, andLgr5).
Cellular and Molecular Gastroenterology and Hepatology. 2020, 9(1), 161-183.
新大院博(医)甲第907号
元資料の権利情報 : 【○!C】 2020 The Authors. Published by Elsevier Inc. on behalf of the AGA Institute. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOIinfo:doi/10.1016/j.jcmgh.2019.08.011
Collection (particular)国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
Date Accepted (W3CDTF)2020-09-07T06:04:08+09:00
Data Provider (Database)国立国会図書館 : 国立国会図書館デジタルコレクション