Plasmacytoid dendritic cells (pDCs) rapidly produce type I interferon (IFN-I) in response to viruses and are essential for antiviral immune responses. Although related to classical dendritic cells (cDCs) in their development and expression profile, pDCs possess many distinct features. Unlike cDCs, pDCs develop in the bone marrow (BM) and emerge into peripheral lymphoid organs and tissues as fully differentiated cells. We now report that pDCs specifically express Runx2, a Runt family transcription factor that is essential for bone development. Runx2-deficient murine pDCs developed normally in the BM but were greatly reduced in the periphery. The defect was cell-intrinsic and was associated with the retention of mature Ly49Q+ pDCs in the BM. Runx2 was required for the expression of several pDC-enriched genes including chemokine receptors Ccr2 and Ccr5. Mature pDCs expressed high levels of Ccr5 at the surface, and Ccr5-deficient pDCs in a competitive setting were reduced in the periphery relative to the BM. Thus, Runx2 is required for the emergence of mature BM pDCs into the periphery, in a process that is partially dependent on Ccr5. These results establish Runx2 as a lineage-specific regulator of immune system development.
Transcription factor Runx2 controls the development and migration of plasmacytoid dendritic cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
ETO family protein Mtg16 regulates the balance of dendritic cell subsets by repressing Id2.
Specimen part, Cell line
View SamplesE protein transcription factors specify major immune cell lineages including lymphocytes and interferon-producing plasmacytoid dendritic cells (pDCs). Corepressors of the ETO family can bind to and block transactivation by E proteins, but the physiological role of these interactions remained unclear. We report that ETO protein Mtg16 binds chromatin primarily through the pDC-specific E protein E2-2 in human pDCs. Mtg16-deficient mice showed impaired pDC development and functionality, whereas the specification of the classical dendritic cells (cDCs) was enhanced. The deletion of Mtg16 caused aberrant expression of E protein antagonist Id2 in pDCs. Thus, Mtg16 acts as a cofactor of E2-2 to promote pDC differentiation and restrict cDC development, revealing an unexpected positive role of ETO proteins in E protein activity.
ETO family protein Mtg16 regulates the balance of dendritic cell subsets by repressing Id2.
Specimen part
View SamplesDermal papilla cells isolated from the human hair follicle are capable of inducing hair growth in recipient epithelia. However, demonstrating disparity from rodent dermal papilla, human cells lose this inductive competance immediately upon growth in culture under normal growth conditions. We grew dermal papilla cells in hanging drop cultures that are morphologically akin to intact dermal papilla, and found that by enhancing the environment for aggregation, we could restore the inductive capacity of human dermal papilla cells in culture. The underlying genes that regulate the inductive potential of dermal papilla cells is not well understood, and we sought to use global profiling to identify key genes and pathways related to inductive competance within dermal papilla cells.
Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth.
Sex, Specimen part, Subject
View SamplesGene expression profiling of scalp skin biopsies from patients with alopecia areata or normal healthy controls
Molecular signatures define alopecia areata subtypes and transcriptional biomarkers.
Sex, Age, Disease, Subject
View SamplesThis goal of these studies were to examine gene expression profiles of skin from patients with alopecia areata undergoing treatment with oral ruxoltinib.
Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata.
Sex, Race, Subject
View SamplesOur goal was to demonstrate the similarity between the original keratinocytes and iPSC-derived keratinocytes from the same individual
Induced pluripotent stem cells from human revertant keratinocytes for the treatment of epidermolysis bullosa.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib.
Specimen part, Treatment, Time
View SamplesThe C3H/HeJ grafted model of alopecia areata was used to determine the efficacy of systemic baricitinib at preventing alopecia or treating established disease.
Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib.
Specimen part, Treatment, Time
View SamplesThe C3H/HeJ grafted model of alopecia areata was used to determine the efficacy of systemic baricitinib at preventing alopecia or treating established disease.
Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib.
Specimen part, Treatment, Time
View Samples