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Chromatin remodeling governs postnatal maturation in dermal fibroblasts [scRNA-Seq]

ABSTRACT: Chromatin remodeling governs postnatal maturation in dermal fibroblasts [scRNA-Seq]

PROVIDER: PRJNA751873 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15338257.fastq.gz	Fastqsanger.gz
	SRR15338258.fastq.gz	Fastqsanger.gz
	SRR15338259.fastq.gz	Fastqsanger.gz
	SRR15338260.fastq.gz	Fastqsanger.gz
	SRR15338261.fastq.gz	Fastqsanger.gz

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Chromatin remodeling governs postnatal maturation in dermal fibroblasts

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Chromatin remodeling governs postnatal maturation in dermal fibroblasts [scRNA-Seq]

Project description:Tissue stem cells preserve a certain level of potency to maintain intact tissue integrity after various injury. Postnatal dermal fibroblasts lose differentiation potential for regenerative healing that recreates normal tissue including functional hair follicles (HFs), however, their intrinsic cellular changes are not understood yet. Here, we uncover a postnatal maturation process in papillary fibroblasts (PFs) mediated by Twist2-driven chromatin and transcriptional remodeling. Within 4 days after birth, dermal PFs lost WNT transcription factors (TFs) and target gene expressions accompanied by loss of H3K27ac expression. Through single-cell transcriptomics, ATAC-seq and ChIP-seq profiling, we define a postnatal maturation trajectory of PFs, in addition to loss of regenerative trajectory, triggered by decrease of H3K27ac and chromatic accessibility. In vivo inhibition of histone deacetylation delays the postnatal chromatin remodeling and maintains developmental signaling and differentiation potential in PFs. TF motif analysis on the chromatin regions losing accessibility identifies TWIST as a potential regulator specifying these regions. Using Twist2 conditional knock-out mouse model, we unearth a postnatal role of Twist2 TF as governing the postnatal maturation process resulting in switch-off of developmental pathways after birth. Together, our findings expose a comprehensive intracellular mechanism driving postnatal maturation in dermal fibroblasts with profound implications for regenerative medicine.

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Chromatin remodeling governs postnatal maturation in dermal fibroblasts [ATAC and ChIP]

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Project description:Dermal fibroblasts deposit type I collagen, the dominant extracellular matrix molecule found in skin, during early postnatal development. Coincident with this biosynthetic program, fibroblasts proteolytically remodel pericellular collagen fibrils by mobilizing the membrane-anchored matrix metalloproteinase, Mmp14. Unexpectedly, dermal fibroblasts in Mmp14-/- mice commit to a large-scale apoptotic program that leaves skin tissues replete with dying cells. A requirement for Mmp14 in dermal fibroblast survival is recapitulated in vitro when cells are embedded within, but not cultured atop, 3-dimensional hydrogels of cross-linked type I collagen. In the absence of Mmp14-dependent pericellular proteolysis, dermal fibroblasts fail to trigger β1 integrin activation and instead actuate a TGF-β1/phospho-JNK stress response that leads to apoptotic cell death in vitro as well as in vivo. Taken together, these studies identify Mmp14 as a requisite cell survival factor that maintains dermal fibroblast viability in postnatal dermal tissues.

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