Abstract：
:DNA crosslinking agents are commonly used in cancer chemotherapy; however, responses of normal tissues to these agents have not been widely investigated. We reveal in mouse interfollicular epidermal, mammary and hair follicle epithelia that genotoxicity does not promote apoptosis but paradoxically induces hyperplasia and fate specification defects in quiescent stem cells. DNA damage to skin causes epithelial and dermal hyperplasia, tissue expansion, and proliferation-independent formation of abnormal K14/K10 dual-positive suprabasal cells. Unexpectedly, this behavior is epithelial cell non-autonomous and independent of an intact immune system. Instead, dermal fibroblasts are both necessary and sufficient to induce the epithelial response, which is mediated by activation of a fibroblast-specific NLRP3 inflammasome and subsequent IL-1β production. Thus, genotoxic agents that are used chemotherapeutically to promote cancer cell death can have the opposite effect on wild-type epithelia by inducing, via a non-autonomous IL-1β-driven mechanism, both hyperplasia and stem cell lineage defects.
journal_name
Dev Celljournal_title
Developmental cellauthors
Seldin L,Macara IGdoi
10.1016/j.devcel.2020.09.021subject
Has Abstractpub_date
2020-12-07 00:00:00pages
558-573.e6issue
5eissn
1534-5807issn
1878-1551pii
S1534-5807(20)30753-Xjournal_volume
55pub_type
杂志文章abstract：:Appropriate patterns of DNA methylation and histone modifications are required to assure cell identity, and their deregulation can contribute to human diseases, such as cancer. Our aim here is to provide an overview of how epigenetic factors, including genomic DNA methylation, histone modifications, and microRNA regul...
journal_title：Developmental cell
pub_type： 杂志文章,评审
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abstract：:Hedgehog (Hh) signaling during development and in postembryonic tissues requires activation of the 7TM oncoprotein Smoothened (Smo) by mechanisms that may involve endogenous lipidic modulators. Exogenous Smo ligands previously identified include the plant sterol cyclopamine (and its therapeutically useful synthetic mi...
journal_title：Developmental cell
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journal_title：Developmental cell
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journal_title：Developmental cell
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journal_title：Developmental cell
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journal_title：Developmental cell
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journal_title：Developmental cell
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journal_title：Developmental cell
pub_type： 评论,杂志文章
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journal_title：Developmental cell
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journal_title：Developmental cell
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journal_title：Developmental cell
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journal_title：Developmental cell
pub_type： 杂志文章
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journal_title：Developmental cell
pub_type： 杂志文章
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pub_type： 杂志文章
doi：10.1016/j.devcel.2005.07.012
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journal_title：Developmental cell
pub_type： 杂志文章,评审
doi：10.1016/j.devcel.2009.02.012
更新日期：2009-03-01 00:00:00
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journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2018.07.023
更新日期：2018-09-24 00:00:00
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journal_title：Developmental cell
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doi：10.1016/j.devcel.2007.09.012
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journal_title：Developmental cell
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journal_title：Developmental cell
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journal_title：Developmental cell
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journal_title：Developmental cell
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journal_title：Developmental cell
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journal_title：Developmental cell
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journal_title：Developmental cell
pub_type： 杂志文章
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journal_title：Developmental cell
pub_type： 杂志文章
doi：10.1016/j.devcel.2012.01.002
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