Bone morphogenetic protein signaling governs biliary‐driven liver regeneration in zebrafish through tbx2b and id2a Article Swipe
Tae‐Young Choi
,
Mehwish Khaliq
,
Shinya Tsurusaki
,
Nikolay Ninov
,
Didier Y. R. Stainier
,
Minoru Tanaka
,
Donghun Shin
·
YOU?
·
· 2017
· Open Access
·
· DOI: https://doi.org/10.1002/hep.29309
YOU?
·
· 2017
· Open Access
·
· DOI: https://doi.org/10.1002/hep.29309
Upon mild liver injury, new hepatocytes originate from preexisting hepatocytes. However, if hepatocyte proliferation is impaired, a manifestation of severe liver injury, biliary epithelial cells (BECs) contribute to new hepatocytes through BEC dedifferentiation into liver progenitor cells (LPCs), also termed oval cells or hepatoblast‐like cells (HB‐LCs), and subsequent differentiation into hepatocytes. Despite the identification of several factors regulating BEC dedifferentiation and activation, little is known about factors involved in the regulation of LPC differentiation into hepatocytes during liver regeneration. Using a zebrafish model of near‐complete hepatocyte ablation, we show that bone morphogenetic protein (Bmp) signaling is required for BEC conversion to hepatocytes, particularly for LPC differentiation into hepatocytes. We found that severe liver injury led to the up‐regulation of genes involved in Bmp signaling, including smad5 , tbx2b , and id2a , in the liver. Bmp suppression did not block BEC dedifferentiation into HB‐LCs; however, the differentiation of HB‐LCs into hepatocytes was impaired due to the maintenance of HB‐LCs in an undifferentiated state. Later Bmp suppression did not affect HB‐LC differentiation but increased BEC number through proliferation. Notably, smad5 , tbx2b , and id2a mutants exhibited similar liver regeneration defects as those observed in Bmp‐suppressed livers. Moreover, BMP2 addition promoted the differentiation of a murine LPC line into hepatocytes in vitro . Conclusions : Bmp signaling regulates BEC‐driven liver regeneration through smad5 , tbx2b , and id2a : it regulates HB‐LC differentiation into hepatocytes through tbx2b and BEC proliferation through id2a ; our findings provide insights into promoting innate liver regeneration as a novel therapy. (H epatology 2017;66:1616–1630).
Related Topics
Concepts
Zebrafish
Bone morphogenetic protein
Regeneration (biology)
Bone morphogenetic protein 2
Liver regeneration
Cell biology
Bone morphogenetic protein 7
Biology
Biochemistry
In vitro
Gene
Metadata
- Type
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- Language
- en
- Landing Page
- https://doi.org/10.1002/hep.29309
- https://aasldpubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep.29309
- OA Status
- bronze
- Cited By
- 50
- References
- 46
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2621585428
All OpenAlex metadata
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https://openalex.org/W2621585428Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1002/hep.29309Digital Object Identifier
- Title
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Bone morphogenetic protein signaling governs biliary‐driven liver regeneration in zebrafish through tbx2b and id2aWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2017Year of publication
- Publication date
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2017-06-09Full publication date if available
- Authors
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Tae‐Young Choi, Mehwish Khaliq, Shinya Tsurusaki, Nikolay Ninov, Didier Y. R. Stainier, Minoru Tanaka, Donghun ShinList of authors in order
- Landing page
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https://doi.org/10.1002/hep.29309Publisher landing page
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https://aasldpubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep.29309Direct link to full text PDF
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YesWhether a free full text is available
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bronzeOpen access status per OpenAlex
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https://aasldpubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep.29309Direct OA link when available
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Zebrafish, Bone morphogenetic protein, Regeneration (biology), Bone morphogenetic protein 2, Liver regeneration, Cell biology, Bone morphogenetic protein 7, Biology, Biochemistry, In vitro, GeneTop concepts (fields/topics) attached by OpenAlex
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50Total citation count in OpenAlex
- Citations by year (recent)
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2025: 5, 2024: 6, 2023: 12, 2022: 7, 2021: 4Per-year citation counts (last 5 years)
- References (count)
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46Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.up‐regulation | 117 |
| abstract_inverted_index.Bmp‐suppressed | 194 |
| abstract_inverted_index.undifferentiated | 161 |
| abstract_inverted_index.dedifferentiation | 32, 59, 141 |
| abstract_inverted_index.hepatoblast‐like | 43 |
| abstract_inverted_index.2017;66:1616–1630). | 257 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 90 |
| corresponding_author_ids | https://openalex.org/A5013543270 |
| countries_distinct_count | 3 |
| institutions_distinct_count | 7 |
| corresponding_institution_ids | https://openalex.org/I170201317, https://openalex.org/I4210155891 |
| citation_normalized_percentile.value | 0.8832431 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |