Msx2 Supports Epidermal Competency during Wound-Induced Hair Follicle Neogenesis

Hughes, Michael W.; Jiang, Ting; Plikus, Maksim V.; Guerrero‐Juarez, Christian F.; Lin, Chien Hong; Schafer, Christopher A.; Maxson, Robert E.; Widelitz, Randall B.

doi:10.1016/j.jid.2018.02.043

Cited by 22 publications

(11 citation statements)

References 39 publications

(77 reference statements)

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“…In contrast, prostaglandin PDG2 inhibits hair follicle neogenesis 16 . Furthermore, WIHN is modulated by several transcriptional regulators, including homeobox factor MSX2 17 , zinc finger protein CXXC5 18 , and RNA-binding protein MSI2 19 . De novo fat regeneration is driven by BMP ligands produced by neogenic hair follicles 5 .…”

Section: Introductionmentioning

confidence: 99%

Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds

et al. 2019

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During wound healing in adult mouse skin, hair follicles and then adipocytes regenerate. Adipocytes regenerate from myofibroblasts, a specialized contractile wound fibroblast. Here we study wound fibroblast diversity using single-cell RNA-sequencing. On analysis, wound fibroblasts group into twelve clusters. Pseudotime and RNA velocity analyses reveal that some clusters likely represent consecutive differentiation states toward a contractile phenotype, while others appear to represent distinct fibroblast lineages. One subset of fibroblasts expresses hematopoietic markers, suggesting their myeloid origin. We validate this finding using single-cell western blot and single-cell RNA-sequencing on genetically labeled myofibroblasts. Using bone marrow transplantation and Cre recombinase-based lineage tracing experiments, we rule out cell fusion events and confirm that hematopoietic lineage cells give rise to a subset of myofibroblasts and rare regenerated adipocytes. In conclusion, our study reveals that wounding induces a high degree of heterogeneity among fibroblasts and recruits highly plastic myeloid cells that contribute to adipocyte regeneration.

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Section: Introductionmentioning

confidence: 99%

Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds

et al. 2019

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“…The single base change present in the Cr2 allele (Chr33: g.7,587,629C>A) is a candidate cis-acting causal mutation for large crest and susceptibility to cerebral hernia because we noted that this mutation results in the creation of predicted binding sites for several transcription factors that have been reported to have a role in hair or skull development: Msx-2 ( Florisson et al 2013 ; Simon et al 2014 ; Hughes et al 2018 ), HOXB13 ( Kömüves et al 2003 ), Dlx-5 ( Depew et al 1999 ; Robledo et al 2002 ; Holleville et al 2007 ), Dlx-3 ( Hwang et al 2008 ; Li et al 2015 ; Whitehouse et al 2019 ) (Supplementary Figure S3). The expansion of the short TG dinucleotide present in the Cr3 allele (Chr33:7,587,694(TG) 7 >(TG) 8 ), is less likely to be functionally important.…”

Section: Discussionmentioning

confidence: 99%

The crest phenotype in domestic chicken is caused by a 195 bp duplication in the intron of HOXC10

Lee

Davis

et al. 2021

G3 Genes|Genomes|Genetics

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The Crest mutation in chicken shows incomplete dominance and causes a spectacular phenotype in which the small feathers normally present on the head are replaced by much larger feathers normally present only in dorsal skin. Using whole genome sequencing, we show that the crest phenotype is caused by a 197 bp duplication of an evolutionarily conserved sequence located in the intron of HOXC10 on chromosome 33. A diagnostic test showed that the duplication was present in all 54 crested chickens representing eight breeds and absent from all 433 non-crested chickens representing 214 populations. The mutation causes ectopic expression of at least five closely linked HOXC genes, including HOXC10, in cranial skin of crested chickens. The result is consistent with the interpretation that the crest feathers are caused by an altered body region identity. The upregulated HOXC gene expression is expanded to skull tissue of Polish chickens showing a large crest often associated with cerebral hernia, but not in Silkie chickens characterized by a small crest, both homozygous for the duplication. Thus, the 197 bp duplication is required for the development of a large crest and susceptibility to cerebral hernia because only crested chicken show this malformation. However, this mutation is not sufficient to cause herniation because this malformation is not present in breeds with a small crest, like Silkie chickens.

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“…Among them, Hsp90α and PDI may be involved in wound repair [ 24 , 25 ], while TAC and EF-1α are possibly related to scar inhibition [ 26 , 27 ]. Msh homeobox 2 is also a pivotal element, further amplifying the Wnt signal integrant to WIHN [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Combination of lyophilized adipose-derived stem cell concentrated conditioned medium and polysaccharide hydrogel in the inhibition of hypertrophic scarring

et al. 2021

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Background Mesenchymal stem cell-based acellular therapies have been widely exploited in managing hypertrophic scars. However, low maintenance dose and transitory therapeutic effects during topical medication remain a thorny issue. Herein, this study aimed to optimize the curative effect of adipose-derived stem cell conditioned medium (ADSC-CM) in the prevention of hypertrophic scarring. Methods In the present study, ADSC-CM was concentrated via the freeze-drying procedure. The efficacy of different dose groups (CM, CM5, CM10) was conducted on the proliferation, apoptosis, and α-smooth muscle actin (α-SMA) expression of human keloid fibroblasts (HKFs) in vitro. Incorporation of adipose-derived stem cell concentrated conditioned medium (ADSCC-CM) into polysaccharide hydrogel was investigated in rabbit ear, in vivo. Haematoxylin-eosin (H&E) and Masson’s trichrome staining were performed for the evaluation of scar hyperplasia. Results We noted that ADSCC-CM could downregulate the α-SMA expression of HKFs in a dose-dependent manner. In the rabbit ear model, the scar hyperplasia in the medium-dose group (CM5) and high-dose group (CM10) was inhibited with reduced scar elevation index (SEI) under 4 months of observation. It is noteworthy that the union of CM5 and polysaccharide hydrogel (CM5+H) yielded the best preventive effect on scar hyperplasia. Briefly, melanin, height, vascularity, and pliability in the CM5+H group were better than those of the control group. Collagen was evenly distributed, and skin appendages could be regenerated. Conclusions Altogether, ADSCC-CM can downregulate the expression of α-SMA due to its anti-fibrosis effect and promote the rearrangement of collagen fibres, which is integral to scar precaution. The in situ cross bonding of ADSCC-CM and polysaccharide hydrogel could remarkably enhance the therapeutic outcomes in inhibiting scar proliferation. Hence, the alliance of ADSCC-CM and hydrogel may become a potential alternative in hypertrophic scar prophylaxis.

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Msx2 Supports Epidermal Competency during Wound-Induced Hair Follicle Neogenesis

Cited by 22 publications

References 39 publications

Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds

Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds

The crest phenotype in domestic chicken is caused by a 195 bp duplication in the intron of HOXC10

Combination of lyophilized adipose-derived stem cell concentrated conditioned medium and polysaccharide hydrogel in the inhibition of hypertrophic scarring

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