Evolution of promoter-proximal pausing enabled a new layer of transcription control.

Promoter-proximal pausing of RNA polymerase II (Pol II) is a key regulatory step during transcription. Despite the central role of pausing in gene regulation, we do not understand the evolutionary processes that led to the emergence of Pol II pausing or its transition to a rate-limiting step actively controlled by transcription factors. Here we analyzed transcription in species across the tree of life.

Dab2 (Disabled-2), an adaptor protein, regulates self-renewal of hair follicle stem cells.

Disabled 2 (Dab2), an adaptor protein, is up regulated in the hair follicle stem cells (HFSCs); however, its role in any tissue stem cells has not been studied. In the present study, we have reported that Dab2 conditional knockout (Dab2-cKO) mice exhibited a delay in the HF cycle due to perturbed activation of HFSCs. Further, Dab2-cKO mice showed a reduction in the number of HFSCs and reduced colony forming ability of HFSCs.

Alk1 acts in non-endothelial VE-cadherin perineurial cells to maintain nerve branching during hair homeostasis.

Vascular endothelial (VE)-cadherin is a well-recognized endothelial cell marker. One of its interacting partners, the TGF-β receptor Alk1, is essential in endothelial cells for adult skin vasculature remodeling during hair homeostasis. Using single-cell transcriptomics, lineage tracing and gene targeting in mice, we characterize the cellular and molecular dynamics of skin VE-cadherin cells during hair homeostasis.

Blood endothelial ALK1-BMP4 signaling axis regulates adult hair follicle stem cell activation.

Blood vessels can play dual roles in tissue growth by transporting gases and nutrients and by regulating tissue stem cell activity via signaling. Correlative evidence implicates skin endothelial cells (ECs) as signaling niches of hair follicle stem cells (HFSCs), but functional demonstration from gene depletion of signaling molecules in ECs is missing to date. Here, we show that depletion of the vasculature-factor Alk1 increases BMP4 secretion from ECs, which delays HFSC activation.

Single-cell transcriptomics of adult skin VE-cadherin expressing lineages during hair cycle.

Adult skin homeostasis involves global reorganization of dermal lineages at different stages of the mouse hair growth cycle. Vascular endothelial cadherin (VE-cadherin encoded by ) expressing cells from blood and lymphatic vasculature structures are known to remodel during the adult hair cycle. Here we employ single-cell RNA-sequencing (scRNA-seq) 10x-genomics analysis of FACS-sorted VE-cadherin expressing cells marked via Cdh5-CreER genetic labeling at resting (telogen) and growth (anagen) stage of hair cycle.

Binary organization of epidermal basal domains highlights robustness to environmental exposure.

Adulte interfollicular epidermis (IFE) renewal is likely orchestrated by physiological demands of its complex tissue architecture comprising spatial and cellular heterogeneity. Mouse tail and back skin display two kinds of basal IFE spatial domains that regenerate at different rates. Here, we elucidate the molecular and cellular states of basal IFE domains by marker expression and single-cell transcriptomics in mouse and human skin.

High-resolution single-cell transcriptomics reveals heterogeneity of self-renewing hair follicle stem cells.

Multipotent bulge stem cells (SCs) fuel the hair follicle (HF) cyclic growth during adult skin homeostasis, but their intrinsic molecular heterogeneity is not well understood. These hair follicle stem cells (HFSCs) engage in bouts of self-renewal, migration and differentiation during the hair cycle. Here, we perform high-resolution single-cell RNA sequencing (scRNA-seq) of HFSCs sorted as CD34 /K14-H2BGFP from mouse skin at mid-anagen, the self-renewal stage.

Publisher Correction: Secretory phospholipase A-IIA overexpressing mice exhibit cyclic alopecia mediated through aberrant hair shaft differentiation and impaired wound healing response.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Context-dependent effect of sPLA-IIA induced proliferation on murine hair follicle stem cells and human epithelial cancer.

Background: Tissue stem cells (SCs) and cancer cells proliferation is regulated by many common signalling mechanisms. These mechanisms temporally balance proliferation and differentiation events during normal tissue homeostasis and repair. However, the effect of these aberrant signalling mechanisms on the ultimate fate of SCs and cancer cells remains obscure.

Establishment and characterization of novel human oral squamous cell carcinoma cell lines from advanced‑stage tumors of buccal mucosa.

Oral squamous cell carcinoma (OSCC) is a leading cause of mortality in India owing to the high percentage of tobacco chewers, smokers and alcohol consumption. OSCC is highly heterogeneous in nature; therefore poses a challenge in the treatment of the patient. To better understand the heterogeneity of the tumors, an in vitro cell line model is required.

Epigenetic control in skin development, homeostasis and injury repair.

Cell-type- and cell-state-specific patterns of covalent modifications on DNA and histone tails form global epigenetic profiles that enable spatiotemporal regulation of gene expression. These epigenetic profiles arise from coordinated activities of transcription factors and epigenetic modifiers, which result in cell-type-specific outputs in response to dynamic environmental conditions and signalling pathways. Recent mouse genetic and functional studies have highlighted the physiological significance of global DNA and histone epigenetic modifications in skin.

Secretory phospholipase A-IIA overexpressing mice exhibit cyclic alopecia mediated through aberrant hair shaft differentiation and impaired wound healing response.

Secretory phospholipase A Group-IIA (sPLA-IIA) is involved in lipid catabolism and growth promoting activity. sPLA-IIA is deregulated in many pathological conditions including various cancers. Here, we have studied the role of sPLA-IIA in the development of cyclic alopecia and wound healing response in relation to complete loss of hair follicle stem cells (HFSCs).

sPLA2 -IIA Overexpression in Mice Epidermis Depletes Hair Follicle Stem Cells and Induces Differentiation Mediated Through Enhanced JNK/c-Jun Activation.

Secretory phospholipase A2 Group-IIA (sPLA2 -IIA) catalyzes the hydrolysis of the sn-2 position of glycerophospholipids to yield fatty acids and lysophospholipids. sPLA2 -IIA is deregulated in various cancers; however, its role in hair follicle stem cell (HFSC) regulation is obscure. Here we report a transgenic mice overexpressing sPLA2 -IIA (K14-sPLA2 -IIA) showed depletion of HFSC pool.