Ets21C sustains a pro-regenerative transcriptional program in blastema cells of Drosophila imaginal discs.
Ets
Ets21C
blastema
gene regulatory network
imaginal disc
regeneration
scRNA-seq
tissue damage
transcription factor
tumors
Journal
Current biology : CB
ISSN: 1879-0445
Titre abrégé: Curr Biol
Pays: England
ID NLM: 9107782
Informations de publication
Date de publication:
08 08 2022
08 08 2022
Historique:
received:
11
08
2021
revised:
06
04
2022
accepted:
14
06
2022
pubmed:
13
7
2022
medline:
12
8
2022
entrez:
12
7
2022
Statut:
ppublish
Résumé
An important unanswered question in regenerative biology is to what extent regeneration is accomplished by the reactivation of gene regulatory networks used during development versus the activation of regeneration-specific transcriptional programs. Following damage, Drosophila imaginal discs, the larval precursors of adult structures, can regenerate missing portions by localized proliferation of damage-adjacent tissue. Using single-cell transcriptomics in regenerating wing discs, we have obtained a comprehensive view of the transcriptome of regenerating discs and identified two regeneration-specific cell populations within the blastema, Blastema1 and Blastema2. Collectively, these cells upregulate multiple genes encoding secreted proteins that promote regeneration including Pvf1, upd3, asperous, Mmp1, and the maturation delaying factor Ilp8. Expression of the transcription factor Ets21C is restricted to this regenerative secretory zone; it is not expressed in undamaged discs. Ets21C expression is activated by the JNK/AP-1 pathway, and it can function in a type 1 coherent feedforward loop with AP-1 to sustain expression of downstream genes. Without Ets21C function, the blastema cells fail to maintain the expression of a number of genes, which leads to premature differentiation and severely compromised regeneration. As Ets21C is dispensable for normal development, these observations indicate that Ets21C orchestrates a regeneration-specific gene regulatory network. We have also identified cells resembling both Blastema1 and Blastema2 in scribble tumorous discs. They express the Ets21C-dependent gene regulatory network, and eliminating Ets21C function reduces tumorous growth. Thus, mechanisms that function during regeneration can be co-opted by tumors to promote aberrant growth.
Identifiants
pubmed: 35820420
pii: S0960-9822(22)01002-8
doi: 10.1016/j.cub.2022.06.040
pmc: PMC9387119
mid: NIHMS1822676
pii:
doi:
Substances chimiques
Drosophila Proteins
0
Egg Proteins
0
Ets21C protein, Drosophila
0
Proto-Oncogene Proteins c-ets
0
Pvf1 protein, Drosophila
0
Transcription Factor AP-1
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3350-3364.e6Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM122490
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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