{"created":"2021-03-01T06:40:26.533238+00:00","id":33998,"links":{},"metadata":{"_buckets":{"deposit":"072102de-2a15-4926-8940-a5dec61930cf"},"_deposit":{"id":"33998","owners":[],"pid":{"revision_id":0,"type":"depid","value":"33998"},"status":"published"},"_oai":{"id":"oai:niigata-u.repo.nii.ac.jp:00033998","sets":["453:455","471:561:562"]},"item_6_alternative_title_1":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_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"}]},"item_6_date_granted_51":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2020-03-23"}]},"item_6_degree_grantor_49":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"新潟大学"}]}]},"item_6_degree_name_48":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(医学)"}]},"item_6_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"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).","subitem_description_type":"Abstract"}]},"item_6_description_5":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"Cellular and Molecular Gastroenterology and Hepatology. 2020, 9(1), 161-183.","subitem_description_type":"Other"}]},"item_6_description_53":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_description":"新大院博(医)甲第907号","subitem_description_type":"Other"}]},"item_6_dissertation_number_52":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"13101甲第4673号"}]},"item_6_full_name_3":{"attribute_name":"著者別名","attribute_value_mlt":[{"nameIdentifiers":[{"nameIdentifier":"177996","nameIdentifierScheme":"WEKO"}],"names":[{"name":"保坂, 和徳"}]}]},"item_6_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"info:doi/10.1016/j.jcmgh.2019.08.011","subitem_relation_type_select":"DOI"}}]},"item_6_rights_15":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"【○!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/)."}]},"item_6_select_19":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_select_item":"ETD"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Hosaka, Kazunori"}],"nameIdentifiers":[{"nameIdentifier":"177995","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-08-31"}],"displaytype":"detail","filename":"r1nmk907.pdf","filesize":[{"value":"11.1 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"本文","url":"https://niigata-u.repo.nii.ac.jp/record/33998/files/r1nmk907.pdf"},"version_id":"47650130-7183-476f-aab4-5e390a726d9c"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-08-31"}],"displaytype":"detail","filename":"r1nmk907_a.pdf","filesize":[{"value":"570.8 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"要旨","url":"https://niigata-u.repo.nii.ac.jp/record/33998/files/r1nmk907_a.pdf"},"version_id":"2aef2662-283a-4530-9c30-8d959ab66dbb"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Hepatocyte","subitem_subject_scheme":"Other"},{"subitem_subject":"Ploidy","subitem_subject_scheme":"Other"},{"subitem_subject":"Zonation","subitem_subject_scheme":"Other"},{"subitem_subject":"Single-Cell PCR","subitem_subject_scheme":"Other"},{"subitem_subject":"Transcriptome","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"thesis","resourceuri":"http://purl.org/coar/resource_type/c_46ec"}]},"item_title":"Transcriptomic Dissection of Hepatocyte Heterogeneity : Linking Ploidy, Zonation, and Stem/Progenitor Cell Characteristics","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Transcriptomic Dissection of Hepatocyte Heterogeneity : Linking Ploidy, Zonation, and Stem/Progenitor Cell Characteristics"}]},"item_type_id":"6","owner":"1","path":["455","562"],"pubdate":{"attribute_name":"公開日","attribute_value":"2020-08-31"},"publish_date":"2020-08-31","publish_status":"0","recid":"33998","relation_version_is_last":true,"title":["Transcriptomic Dissection of Hepatocyte Heterogeneity : Linking Ploidy, Zonation, and Stem/Progenitor Cell Characteristics"],"weko_creator_id":"1","weko_shared_id":null},"updated":"2022-12-15T04:04:17.853185+00:00"}