YAP1 increases organ size and expands undifferentiated progenitor cells
Open accessAbstract
The mechanisms that regulate mammalian organ size are poorly understood. It is unclear whether the pathways that control organ size also impinge on stem/progenitor cells. A highly expressed gene in stem cells is YAP1, the ortholog of Drosophila Yorkie, a downstream component of the Hippo pathway. Mutations in components of this pathway produce tissue overgrowth phenotypes in the fly whereas mammalian orthologs, like salvador, merlin, LATS, and YAP1, have been implicated in tumorigenesis. We report here that YAP1 increases organ size and causes aberrant tissue expansion in mice. YAP1 activation reversibly increases liver size more than 4-fold. In the intestine, expression of endogenous YAP1 is restricted to the progenitor/stem cell compartment, and activation of YAP1 expands multipotent undifferentiated progenitor cells, which differentiate upon cessation of YAP1 expression. YAP1 stimulates Notch signaling, and administration of gamma-secretase inhibitors suppressed the intestinal dysplasia caused by YAP1. Human colorectal cancers expressing higher levels of YAP1 share molecular aspects with YAP1-induced dysplastic growth in the mouse. Our data show that the Hippo signaling pathway regulates organ size in mammals and can act on stem cell compartments, indicating a potential link between stem/progenitor cells, organ size, and cancer.
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Activated YAP signalling reversibly increased liver size, but its deletion did not affect liver size during homeostasis.
“While activated YAP signalling reversibly increased liver size,93 its deletion did not affect liver size during homeostasis.57,58,94”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [93]
The Hippo pathway controls liver size and is commonly amplified in human hepatocellular carcinoma.
“This pathway controls liver size and is commonly amplified in human hepatocellular carcinoma (Camargo et al., 2007; Zender et al., 2006).”
From Hippo Signaling Influences HNF4A and FOXA2 Enhancer Switching during Hepatocyte Differentiation (2014) · cites this paper as Camargo et al., 2007
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- Authors
- Camargo, F. D., Gokhale, S., Johnnidis, J. B., Fu, D., Bell, G. W., Jaenisch, R., & Brummelkamp, T. R.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Camargo, Fernando D.
- Brummelkamp, Thijn R.
- ORCID
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 17
- Issue
- 23
- Pages
- 2054-2060
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2159376228
- Cited by
- 1,252
- References
- 1
- Citations by year
- 2026: 39 · 2025: 50 · 2024: 59 · 2023: 55 · 2022: 95 · 2021: 89 · 2020: 95 · 2019: 87 · 2018: 95 · 2017: 76 · 2016: 76 · 2015: 110 · 2014: 85 · 2013: 65 · 2012: 58
- FWCI
- 11.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA84198)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- YAP, Hippo signaling pathway, organ size control, tissue overgrowth, Notch signaling, gamma-secretase inhibitors, intestinal dysplasia, colorectal cancer, liver size, Yorkie
- MeSH terms
- YAP-Signaling Proteins, Adenoma, Animals, Cell Differentiation, Humans, Intestine, Small, Liver, Mice, Transgenic, Organ Size, Phosphoproteins, Stem Cells, Transcription Factors, Colorectal Neoplasms, Signal Transduction, Oligonucleotide Array Sequence Analysis, Adaptor Proteins, Signal Transducing, Cell Proliferation, Mice
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