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Two succeeding fibroblastic lineages drive dermal development and the transition from regeneration to scarring

Jiang, Dongsheng; Correa-Gallegos, Donovan; Christ, Simon; Stefanska, Ania; Liu, Juan; Ramesh, Pushkar; Rajendran, Vijayanand; De Santis, Martina M. LU ; Wagner, Darcy E. LU and Rinkevich, Yuval (2018) In Nature Cell Biology 20(4). p.422-431
Abstract

During fetal development, mammalian back-skin undergoes a natural transition in response to injury, from scarless regeneration to skin scarring. Here, we characterize dermal morphogenesis and follow two distinct embryonic fibroblast lineages, based on their history of expression of the engrailed 1 gene. We use single-cell fate-mapping, live three dimensional confocal imaging and in silico analysis coupled with immunolabelling to reveal unanticipated structural and regional complexity and dynamics within the dermis. We show that dermal development and regeneration are driven by engrailed 1-history-naive fibroblasts, whose numbers subsequently decline. Conversely, engrailed 1-history-positive fibroblasts possess scarring abilities at this... (More)

During fetal development, mammalian back-skin undergoes a natural transition in response to injury, from scarless regeneration to skin scarring. Here, we characterize dermal morphogenesis and follow two distinct embryonic fibroblast lineages, based on their history of expression of the engrailed 1 gene. We use single-cell fate-mapping, live three dimensional confocal imaging and in silico analysis coupled with immunolabelling to reveal unanticipated structural and regional complexity and dynamics within the dermis. We show that dermal development and regeneration are driven by engrailed 1-history-naive fibroblasts, whose numbers subsequently decline. Conversely, engrailed 1-history-positive fibroblasts possess scarring abilities at this early stage and their expansion later on drives scar emergence. The transition can be reversed, locally, by transplanting engrailed 1-naive cells. Thus, fibroblastic lineage replacement couples the decline of regeneration with the emergence of scarring and creates potential clinical avenues to reduce scarring.

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author
organization
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type
Contribution to journal
publication status
published
subject
in
Nature Cell Biology
volume
20
issue
4
pages
10 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85044533617
ISSN
1465-7392
DOI
10.1038/s41556-018-0073-8
language
English
LU publication?
yes
id
9fb8a05b-54fd-43bb-b5d3-593aa192f514
date added to LUP
2018-04-10 12:20:56
date last changed
2019-10-15 06:35:09
@article{9fb8a05b-54fd-43bb-b5d3-593aa192f514,
  abstract     = {<p>During fetal development, mammalian back-skin undergoes a natural transition in response to injury, from scarless regeneration to skin scarring. Here, we characterize dermal morphogenesis and follow two distinct embryonic fibroblast lineages, based on their history of expression of the engrailed 1 gene. We use single-cell fate-mapping, live three dimensional confocal imaging and in silico analysis coupled with immunolabelling to reveal unanticipated structural and regional complexity and dynamics within the dermis. We show that dermal development and regeneration are driven by engrailed 1-history-naive fibroblasts, whose numbers subsequently decline. Conversely, engrailed 1-history-positive fibroblasts possess scarring abilities at this early stage and their expansion later on drives scar emergence. The transition can be reversed, locally, by transplanting engrailed 1-naive cells. Thus, fibroblastic lineage replacement couples the decline of regeneration with the emergence of scarring and creates potential clinical avenues to reduce scarring.</p>},
  author       = {Jiang, Dongsheng and Correa-Gallegos, Donovan and Christ, Simon and Stefanska, Ania and Liu, Juan and Ramesh, Pushkar and Rajendran, Vijayanand and De Santis, Martina M. and Wagner, Darcy E. and Rinkevich, Yuval},
  issn         = {1465-7392},
  language     = {eng},
  month        = {04},
  number       = {4},
  pages        = {422--431},
  publisher    = {Nature Publishing Group},
  series       = {Nature Cell Biology},
  title        = {Two succeeding fibroblastic lineages drive dermal development and the transition from regeneration to scarring},
  url          = {http://dx.doi.org/10.1038/s41556-018-0073-8},
  volume       = {20},
  year         = {2018},
}