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Hepatic reprogramming occurs in a time-independent manner via an initial asymmetric division and continued mitotic activity.

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Title: Hepatic reprogramming occurs in a time-independent manner via an initial asymmetric division and continued mitotic activity.
Authors: Goto N; Division of Organogenesis and Regeneration, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan., Miura S; Division of Organogenesis and Regeneration, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; Division of Stem Cell Medicine, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan., Kawamata M; Division of Organogenesis and Regeneration, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan., Horisawa K; Division of Organogenesis and Regeneration, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan., Suzuki R; Division of Organogenesis and Regeneration, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan., Miyata T; Division of Organogenesis and Regeneration, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan., Taniguchi N; Division of Organogenesis and Regeneration, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan., Suzuki A; Division of Organogenesis and Regeneration, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: suzukicks@bioreg.kyushu-u.ac.jp.
Source: Stem cell reports [Stem Cell Reports] 2026 Sep 08; Vol. 21 (9), pp. 103056. Date of Electronic Publication: 2026 Aug 27.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Cell Press Country of Publication: United States NLM ID: 101611300 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2213-6711 (Electronic) Linking ISSN: 22136711 NLM ISO Abbreviation: Stem Cell Reports Subsets: MEDLINE
Imprint Name(s): Original Publication: [Cambridge, MA] : Cell Press, c 2013-
MeSH Terms: Cellular Reprogramming*/genetics , Hepatocytes*/cytology , Hepatocytes*/metabolism , Mitosis* , Asymmetric Cell Division*, Fibroblasts/cytology ; Fibroblasts/metabolism ; Animals ; Time-Lapse Imaging ; Mice ; Time Factors
Abstract: Recent advancements in cellular reprogramming make it possible to alter cell fate, yet its mechanisms remain largely unclear. While previous studies have explored the link between cell division and reprogramming, it is still unknown why some cells reprogram under identical conditions, while others do not. In this study, we used the direct reprogramming of fibroblasts into induced hepatocyte-like cells (iHepCs) as a model to address this issue. Time-lapse imaging was performed throughout the entire reprogramming process, from the introduction of reprogramming factors to the completion of iHepC conversion. Spatiotemporal single-cell tracking revealed that the direct hepatic reprogramming follows a hybrid model, combining elite and stochastic models. Elite-like cells emerge from the earliest cell divisions, undergo random selection, and successfully reprogram a subset of their descendants. Moreover, cells that ultimately become iHepCs exhibited active division both before and after reprogramming. These results suggest that targeting active cell division may enhance reprogramming efficiency.
(Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved.)
Competing Interests: Declaration of interests The authors declare no competing interests.
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Contributed Indexing: Keywords: cell division; direct reprogramming; hepatocyte; single-cell tracking; time-lapse imaging
Entry Date(s): Date Created: 20260827 Date Completed: 20260908 Latest Revision: 20260914
Update Code: 20260914
PubMed Central ID: PMC13555477
DOI: 10.1016/j.stemcr.2026.103056
PMID: 42660117
Database: MEDLINE
Description
ISSN:2213-6711
DOI:10.1016/j.stemcr.2026.103056