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Dynamics of hepatocyte-cholangiocyte cell-fate decisions during liver development and regeneration

Sahoo, S and Mishra, A and Diehl, AM and Jolly, MK (2022) Dynamics of hepatocyte-cholangiocyte cell-fate decisions during liver development and regeneration. In: iScience, 25 (9).

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Official URL: https://doi.org/10.1016/j.isci.2022.104955


The immense regenerative potential of the liver is attributed to the ability of its two key cell types – hepatocytes and cholangiocytes – to trans-differentiate to one another either directly or through intermediate progenitor states. However, the dynamic features of decision-making between these cell-fates during liver development and regeneration remains elusive. Here, we identify a core gene regulatory network comprising c/EBPα, TGFBR2, and SOX9 which is multistable in nature, enabling three distinct cell states – hepatocytes, cholangiocytes, and liver progenitor cells (hepatoblasts/oval cells) – and stochastic switching among them. Predicted expression signature for these three states are validated through multiple bulk and single-cell transcriptomic datasets collected across developmental stages and injury-induced liver repair. This network can also explain the experimentally observed spatial organization of phenotypes in liver parenchyma and predict strategies for efficient cellular reprogramming. Our analysis elucidates how the emergent dynamics of underlying regulatory networks drive diverse cell-fate decisions in liver development and regeneration.

Item Type: Journal Article
Publication: iScience
Publisher: Elsevier Inc.
Additional Information: The copyright for this article belongs to Elsevier Inc.
Keywords: Cell biology; In silico biology; Systems biology
Department/Centre: Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
UG Programme
Division of Physical & Mathematical Sciences > Physics
Date Deposited: 08 Oct 2022 04:06
Last Modified: 08 Oct 2022 04:06
URI: https://eprints.iisc.ac.in/id/eprint/77288

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