Keratin 14 is a novel interaction partner of keratinocyte differentiation regulator: receptor-interacting protein kinase 4

Sümer, Ceren; Er, Asiye Büşra Boz; Dinçer, Tuba

doi:10.3906/biy-1904-37

Cited by 17 publications

(12 citation statements)

References 34 publications

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“…Finally, the present study can clarify why zebrafish blastema regeneration is epithelial-dependent (Wang et al, 2012;Zhang et al, 2015), and how undergo EMT (Lepilina et al, 2006). Our data showed that the epithelial-predominant keratin could help cell to bridge mechanosignaling between extracellular-cytoplasmic signal transductions and histone modifications-mediated chromatin remodeling, thus supporting the view that the keratin could modulate IF-cytoskeleton organization, interact with focal adhesions and cell-surface molecules (Quinlan et al, 2017;Sumer et al, 2019). By in vitro culture of zebrafish embryonic fibroblast cells, we demonstrated that the keratin 5 network could modulate H3K9Ac/Me3 chromatin state and expression of three core blastema tissue specific genes through the noncanonical BMP4 signaling pathway (Fig.5C).…”

Section: Discussionsupporting

confidence: 75%

Keratin5-BMP4 mechanosignaling regulates reciprocal acetylation and methylation at H3K9 to define blastema cell remodeling during zebrafish heart regeneration

Wang

Guo

et al. 2020

Preprint

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Heart regeneration after myocardial infarction remains challenging due to scar and ischemia-reperfusion injury. Here, we show that zebrafish blastema regeneration can effectively resalvage the wound myocardium and blood clot through cytoplasmic exocytosis and nuclear reorganization. The cell remodeling process are also visualized by spatiotemporal expression of three core blastema genes: alpha-SMA- which marks for fibrogenesis, Flk1for angiogenesis/hematopoiesis, Pax3a for remusculogensis, and by characteristic chromatin depositions of H3K9Ac/H3K9Me3. Genome-wide enhancer identification links the depositions of the two histone marks to the chromatin state and these three core blastema cell phenotypes. When the blastema subcellular fractions are introduced into the cultured zebrafish embryonic fibroblasts the altered transcription profile is comparable to the blastema transcription in terms of extracellular matrix structural constituent, vasculature development/angiogenesis, and cardiac muscle regeneration. From the subcellular fractions we identify 15 extracellular components and intermediate filaments, and show that introduction of human Krt5 and noggin peptides conversely regulate PAC2 cells F-actin reorganization, chromatin depositions of H3K9Ac/ H3K9Me3 and phosphorylation of Smad, which are accompanied by characteristic transcriptions of bmp, bmp4, three core blastema genes as well as specific histone acetylation/methylation-related genes. Collectively, this study establishes a new Krt5-BMP4 mechanosignaling cascade that links extracellular molecules to chromatin modifications and regulates blastema cell remodeling, thus providing mechanistic insights into the mesoderm-derived blastema regeneration and underlining a therapy strategy for myocardial infarction.

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Section: Discussionsupporting

confidence: 75%

Keratin5-BMP4 mechanosignaling regulates reciprocal acetylation and methylation at H3K9 to define blastema cell remodeling during zebrafish heart regeneration

Wang

Guo

et al. 2020

Preprint

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“…As the most abundant skin cell type, EpD accounted for 37.96% (9201 cells) of all skin cells, which could be divided into nine different clusters, including three basal cell types (EpD_Basal1–3) majorly expressing basal epithelium markers KRT5, KRT14, ITGA6, and ITGB1; four epithelial differentiated cell types (EpD_Spinous, EpD_Granualr/spinous, EpD_Granular, EpD_Corneum) majorly recognized by epithelial differentiation marker KRT10, KRT1, and GRHL1 (ref. 20 – 23 ); sebaceous gland (EpD_SG) expressing APOC1, ACSL5, ABCC3 (ref. 24 ); follicles (EpD_Foli) expressing CD200, SOX9, KRT19 (ref.…”

Section: Resultsmentioning

confidence: 99%

Single cell transcriptional zonation of human psoriasis skin identifies an alternative immunoregulatory axis conducted by skin resident cells

et al. 2021

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Psoriasis is the most common skin disease in adults. Current experimental and clinical evidences suggested the infiltrating immune cells could target local skin cells and thus induce psoriatic phenotype. However, recent studies indicated the existence of a potential feedback signaling loop from local resident skin cells to infiltrating immune cells. Here, we deconstructed the full-thickness human skins of both healthy donors and patients with psoriasis vulgaris at single cell transcriptional level, and further built a neural-network classifier to evaluate the evolutional conservation of skin cell types between mouse and human. Last, we systematically evaluated the intrinsic and intercellular molecular alterations of each cell type between healthy and psoriatic skin. Cross-checking with psoriasis susceptibility gene loci, cell-type based differential expression, and ligand-receptor communication revealed that the resident psoriatic skin cells including mesenchymal and epidermis cell types, which specifically harbored the target genes of psoriasis susceptibility loci, intensively evoked the expression of major histocompatibility complex (MHC) genes, upregulated interferon (INF), tumor necrosis factor (TNF) signalling and increased cytokine gene expression for primarily aiming the neighboring dendritic cells in psoriasis. The comprehensive exploration and pathological observation of psoriasis patient biopsies proposed an uncovered immunoregulatory axis from skin local resident cells to immune cells, thus provided a novel insight for psoriasis treatment. In addition, we published a user-friendly website to exhibit the transcriptional change of each cell type between healthy and psoriatic human skin.

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“…Newly produced cells gradually differentiate and mature into keratinocytes, move toward upper layers and comprise the epidermal tissue [ 37 ]. To examine whether GREM2 expression and the differentiation level in the epidermis are correlated, immunohistochemistry was performed against GREM2, an epidermal undifferentiation marker KRT14 and an epidermal differentiation marker KRT10 [ 38 , 39 ] on human skin sections (n = 14), and expression levels were analyzed. Since our previous study showed that GREM2 expression levels prominently varied among elderly individuals [ 18 ], we examined skin samples from the elderly (65–89 years of age).…”

Section: Resultsmentioning

confidence: 99%

Gremlin 2 suppresses differentiation of stem/progenitor cells in the human skin

Kawagishi‐Hotta

Hasegawa

Inoue

et al. 2021

Regenerative Therapy

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Introduction The skin is comprised of various kinds of cells and has three layers, the epidermis, dermis and subcutaneous adipose tissue. Stem cells in each tissue duplicate themselves and differentiate to supply new cells that function in the tissue, and thereby maintain the tissue homeostasis. In contrast, senescent cells accumulate with age and secrete senescence-associated secretory phenotype (SASP) factors that impair surrounding cells and tissues, which lowers the capacity to maintain homeostasis in each tissue. Previously, we found Gremlin 2 (GREM2) as a novel SASP factor in the skin and reported that GREM2 suppressed the differentiation of adipose-derived stromal/stem cells. In the present study, we investigated the effects of GREM2 on stem cells in the epidermis and dermis. Methods To examine whether GREM2 expression and the differentiation levels in the epidermis and dermis are correlated, the expressions of GREM2, stem cell markers, an epidermal differentiation marker Keratin 10 (KRT10) and a dermal differentiation marker type 3 procollagen were examined in the skin samples (n = 14) randomly chosen from the elderly where GREM2 expression level is high and the individual differences of its expression are prominent. Next, to test whether GREM2 affects the differentiation of skin stem cells, cells from two established lines (an epidermal and a dermal stem/progenitor cell model) were cultured and induced to differentiate, and recombinant GREM2 protein was added. Results In the human skin, the expression levels of GREM2 varied among individuals both in the epidermis and dermis. The expression level of GREM2 was not correlated with the number of stem cells, but negatively correlated with those of both an epidermal and a dermal differentiation markers. The expression levels of epidermal differentiation markers were significantly suppressed by the addition of GREM2 in the three-dimensional (3D) epidermis generated with an epidermal stem/progenitor cell model. In addition, by differentiation induction, the expressions of dermal differentiation markers were induced in cells from a dermal stem/progenitor cell model, and the addition of GREM2 significantly suppressed the expressions of the dermal differentiation markers. Conclusions GREM2 expression level did not affect the numbers of stem cells in the epidermis and dermis but affects the differentiation and maturation levels of the tissues, and GREM2 suppressed the differentiation of stem/progenitor cells in vitro . These findings suggest that GREM2 may contribute to the age-related reduction in the capacity to maintain skin homeostasis by suppressing the differentiation of epidermal and dermal stem/progenitor cells.

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Keratin 14 is a novel interaction partner of keratinocyte differentiation regulator: receptor-interacting protein kinase 4

Cited by 17 publications

References 34 publications

Keratin5-BMP4 mechanosignaling regulates reciprocal acetylation and methylation at H3K9 to define blastema cell remodeling during zebrafish heart regeneration

Keratin5-BMP4 mechanosignaling regulates reciprocal acetylation and methylation at H3K9 to define blastema cell remodeling during zebrafish heart regeneration

Single cell transcriptional zonation of human psoriasis skin identifies an alternative immunoregulatory axis conducted by skin resident cells

Gremlin 2 suppresses differentiation of stem/progenitor cells in the human skin

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