2019
DOI: 10.1038/s41467-019-11880-9
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SOX11 and SOX4 drive the reactivation of an embryonic gene program during murine wound repair

Abstract: Tissue injury induces changes in cellular identity, but the underlying molecular mechanisms remain obscure. Here, we show that upon damage in a mouse model, epidermal cells at the wound edge convert to an embryonic-like state, altering particularly the cytoskeletal/extracellular matrix (ECM) components and differentiation program. We show that SOX11 and its closest relative SOX4 dictate embryonic epidermal state, regulating genes involved in epidermal development as well as cytoskeletal/ECM organization. Corre… Show more

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Cited by 71 publications
(48 citation statements)
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“…The strong induction of 9 MARCKSL1 upon SOX11 overexpression (log2 fold change 5.88) ( Fig. S4c), an important regulator of actin stability and migration in neurons 19 , and the SOX11 regulated genes FSCN1 and TEAD2, two published SOX11 targets involved in cytoskeleton and neurodevelopment 7,20 , further supports the observed enriched gene sets.…”
Section: The Sox11 Regulated Transcriptome Is Involved In Epigeneticsupporting
confidence: 66%
“…The strong induction of 9 MARCKSL1 upon SOX11 overexpression (log2 fold change 5.88) ( Fig. S4c), an important regulator of actin stability and migration in neurons 19 , and the SOX11 regulated genes FSCN1 and TEAD2, two published SOX11 targets involved in cytoskeleton and neurodevelopment 7,20 , further supports the observed enriched gene sets.…”
Section: The Sox11 Regulated Transcriptome Is Involved In Epigeneticsupporting
confidence: 66%
“…Aging-associated destruction of joints and cartilage degradation in osteoarthritis is correlated with changes in extracellular matrix of articular cartilage, such as cartilage ECM stiffness, and in the levels and solubility profiles of matrix crosslinks, especially pentosidine, as well as reduced thickness of cartilage, proteolysis, advanced glycation and calcification (Eyre et al, 1988;Pokharna et al, 1995;Lotz and Loeser, 2012). Notably, rejuvenation has emerged as a promising therapeutic regenerative approach for improvement or restoration of the self-repair capacity of injured or aging tissue and organ systems (Leung et al, 2006;Nelson et al, 2008;Luria and Chu, 2014;Sarkar et al, 2020), which has been proposed as a conversion into an embryonic-like state recapitulating many events during embryogenesis, including the reactivation of embryonic signature genes, and cytoskeletal/ECM components, and lineage specification (Vortkamp et al, 1998;Jankowski et al, 2009;Luo et al, 2009;Adam et al, 2015;Caldwell and Wang, 2015;Hu et al, 2017;Ransom et al, 2018;Feng et al, 2019;Lin W. et al, 2019;Miao et al, 2019). Consistently, the process of cartilage repair has been considered as recapitulation of various events during developmental morphogenesis.…”
Section: Potential Links Between Lox and Aging-associated Cartilage Dmentioning
confidence: 99%
“…iSOX11 DCIS cells grown in 3D showed enrichment of genes regulating ECM disassembly, collagen biosynthesis, glycosaminoglycan metabolism, and platelet degranulation ( Figure 3—figure supplement 1 and Supplementary file 3 ). Platelet activation is one of the first steps of tissue repair as part of the wound healing process and Sox4 and Sox11 have recently been shown to reactivate an embryonic epidermal programme during wound repair in mice ( Miao et al, 2019 ). We found substantial overlap of the embryonic wound signature that was shown to be directly regulated by Sox11 and Sox4 ( Miao et al, 2019 ) with iSOX11 spheroids ( Table 1 ).…”
Section: Resultsmentioning
confidence: 99%
“…Platelet activation is one of the first steps of tissue repair as part of the wound healing process and Sox4 and Sox11 have recently been shown to reactivate an embryonic epidermal programme during wound repair in mice ( Miao et al, 2019 ). We found substantial overlap of the embryonic wound signature that was shown to be directly regulated by Sox11 and Sox4 ( Miao et al, 2019 ) with iSOX11 spheroids ( Table 1 ). In particular, we detected upregulation of embryonic wound signature components with links to actin polymerisation and cell adhesion, and one known regulator of embryonic stem cell pluripotency, RCOR2, which can function with other transcription factors to induce pluripotent stem cells ( Figure 3—figure supplement 1 ; Yang et al, 2011 ).…”
Section: Resultsmentioning
confidence: 99%