RIPK4 but not the related kinases RIPK1, RIPK2, and RIPK3 caused similar transcriptional changes to Wnt3a. Overall design: PA1 cells were transfected by 8ug RIPK1, RIPK2, RIPK3, or RIPK4 for 48h, RNA were extracted and sequenced.
Phosphorylation of Dishevelled by protein kinase RIPK4 regulates Wnt signaling.
Cell line, Subject
View SamplesCanonical WNT-signaling is essential for placode formation irrespective of appendage type. At sites of placode initiation, Although WNT-signaling occurs in both epithelium and mesenchyme, the site of most intense activity as revealed by the WNT reporter Axin2-LacZ was in a zone just below the epithelial-mesenchymal interface. In ventral foot-skin, this WNT activity peaked at E17.5, concomitant with sweat bud fate commitment, while in dorsal back-skin, it began at E14.5, concomitant with HF fate specification. Overall design: To address whether WNT-signaling within this zone might regionally influence the transcriptional landscape of body-site mesenchymes to support distinct epithelial fates, we transcriptionally profiled the Axin2-positive and Axin2-negative dermal cells following their FACS-purification from E17.5 ventral foot-skin and E14.5 dorsal back-skin
Spatiotemporal antagonism in mesenchymal-epithelial signaling in sweat versus hair fate decision.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Specific microRNAs are preferentially expressed by skin stem cells to balance self-renewal and early lineage commitment.
Sex, Specimen part, Treatment
View SamplesIncreasing evidence suggests that microRNAs may play important roles in regulating self-renewal and differentiation in mammalian stem cells (SCs). Here, we explore this issue in skin. We first characterize microRNA expression profiles of skin SCs versus their committed proliferative progenies and identify a microRNA subset associating with stemness. Of these, miR-125b is dramatically downregulated in early SC-progeny. We engineer an inducible mice system and show that when miR-125b is sustained in SC-progenies, tissue balance is reversibly skewed towards stemness at the expense of epidermal, oil-gland and HF differentiation. Using gain-and-loss of function in vitro, we further implicate miR-125b as a repressor of SC differentiation. In vivo, transcripts repressed upon miR-125b induction are enriched >700% for predicted miR-125b targets normally downregulated upon SC-lineage commitment. We verify some of these miR-125b targets, and show that Blimp1 and VDR in particular can account for many tissue imbalances we see when miR-125b is deregulated.
Specific microRNAs are preferentially expressed by skin stem cells to balance self-renewal and early lineage commitment.
Sex, Specimen part, Treatment
View SamplesIn adult skin, each hair follicle contains a reservoir of stem cells (the bulge), which can be mobilized to regenerate the new follicle with each hair cycle and to reepithelialize epidermis during wound repair. Here we report new methods that permit their clonal analyses and engraftment and demonstrate the two defining features of stem cells, namely self-renewal and multi-potency. We also show that, within the bulge, there are two distinct populations, one of which maintains basal lamina contact and temporally precedes the other, which is suprabasal and arises only after the start of the first postnatal hair cycle. This spatial distinction endows them with discrete transcriptional programs, but surprisingly, both populations are growth inhibited in the niche but can self-renew in vitro and make epidermis and hair when grafted. These findings suggest that the niche microenvironment imposes intrinsic stemness features without restricting the establishment of epithelial polarity and changes in gene expression.
Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche.
Specimen part
View SamplesMouse hair follicles undergo synchronized cycles. Cyclical regeneration and hair growth is fueled by hair follicle stem cells (HFSCs). HFSCs regenerate hair in response to canonical Wnt signalling. We used RNA-seq to unfold genome-wide chromatin landscapes of ß-catenin within the native HFSC-niche. Overall design: ß-catenin control and cKO hair follicle stem cells (HFSCs) at the onset of anagen skins were FACS-purified for RNA-sequcencing. Telogen quiescent hair follicle stem cells (HFSCs) were FACS-purified for ChIP-sequcencing. Telogen>anagen activated bulge hair follicle stem cells (HFSCs) were FACS-purified for RNA-sequcencing.
In vivo transcriptional governance of hair follicle stem cells by canonical Wnt regulators.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Ikaros mediates gene silencing in T cells through Polycomb repressive complex 2.
Specimen part, Cell line
View SamplesSweat glands are abundant glands of our body and essential for thermoregulation. Like mammary glands, they originate from epidermal progenitors. However, they display few signs of cellular turnover, and whether they have stem cells and tissue regenerative capacity remain largely unexplored. Here we address these issues. Using lineage-tracing, we identify multipotent progenitors in sweat duct that transition to unipotency after developing the sweat gland. In characterizing four adult stem cell populations of glandular skin, we show that they display distinct regenerative capabilities and remain unipotent when healing epidermal, myoepithelial-specific and luminal-specific injuries. We devise purification schemes, isolate and transcriptionally profile progenitors. Exploiting molecular differences between sweat and mammary glands, we show that only some progenitors regain multipotency to produce de novo ductal and glandular structures, but that these can retain their identity even within certain foreign microenvironments. Our findings provide new concepts about glandular stem cells and sweat gland biology.
Identification of stem cell populations in sweat glands and ducts reveals roles in homeostasis and wound repair.
Sex, Specimen part
View SamplesMouse hair follicles (HFs) undergo synchronized cycles. Cyclical regeneration and hair growth is fueled by stem cells (SCs). During the rest phase, the HF-SCs remain quiescent due to extrinsic inhibitory signals within the niche. As activating cues accumulate, HF-SCs become activated, proliferate, and grow downward to form transient-amplifying matrix progenitor cells. We used microarrays to detect the relative levels of global gene expression underlying the states of hair follicle stem cells and their transient-amplifying progeny before differentiation.
Genome-wide maps of histone modifications unwind in vivo chromatin states of the hair follicle lineage.
Sex, Specimen part
View SamplesThe Ikaros zink finger transcription factor is a critical regulator of the hematopietic system, and plays an important role in the regulation of the development and function of several blood cell lineages.
Ikaros mediates gene silencing in T cells through Polycomb repressive complex 2.
Specimen part
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