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Gene expression profiling of CD45+CD3-CD11b+MHCII+ subsets in P5 (day 5 after birth) and 1.5M (1.5 months after birth) mouse epidermal cells

ABSTRACT: The primary Langerhans cells (LCs) network in the mouse skin epidermis is established within a week after birth by differentiation of skin-seeded embryonic LC precursors into mature LCs. Through binding to distinct receptors, two members of the TGFβ superfamily, BMP7 and TGFβ1, initiate cellular signaling essential for inducing LCs differentiation and for preserving LCs in a quiescent state, respectively. However, how these two processes are regulated remains elusive. Here we show that loss of Cbfβ2, one of two RNA splice variants of the Cbfb gene, results in long-term persistence of embryonic-derived immature LCs after their developmental arrest at the transition into the EpCAM+ stage. This phenotype is caused by selective loss of TGFβ receptor signaling, essential for LCs differentiation with intact signaling, which maintains the quiescent state. Interestingly, skin residential Cbfβ2-defcient LC precursors could differentiate further upon transgenic Cbfβ2 expression, but only around postnatal period and not when it was expressed in one month old mice. Loss of developmental potency in the precursor cells was accompanied by diminished BMP7-BMPR1A signaling. Collectively, our results reveal an essential and selective requirement for the Cbfβ2 variant in LC differentiation, and provide a novel insight into how establishment and homeostasis of the LCs network is regulated.

ORGANISM(S): Mus musculus

PROVIDER: GSE95487 | GEO | 2017/08/14

SECONDARY ACCESSION(S): PRJNA377256

REPOSITORIES: GEO

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Project description:The ontogeny of human Langerhans cells (LCs) remains poorly characterized, in particular the nature of LC precursors and the factors that may drive LC differentiation. Through a systematic transcriptomic analysis of TSLP-activated dendritic cells (DCs), we unexpectedly identified markers that have been associated with a skin-homing potential as well as with a LC phenotype. We performed transcriptomic analysis of TSLP-activated blood DCs, as compared to freshly purified, Medium-, and TNF-activated DCs. Among TSLP up-regulated genes, we identified molecules associated with skin homing, LC phenotype, and LC function, as determined by a literature-based survey. Conversely, genes not expressed in LCs were not found among TSLP-induced genes. Further experiments showed that TGF-? synergized with TSLP leading to the differentiation of blood BDCA-1+ DCs into bona fide Birbeck granule-positive LCs. The ontogeny of human Langerhans cells (LCs) remains poorly characterized, in particular the nature of LC precursors and the factors that may drive LC differentiation. Through a systematic transcriptomic analysis of TSLP-activated dendritic cells (DCs), we unexpectedly identified markers that have been associated with a skin-homing potential as well as with a LC phenotype. We performed transcriptomic analysis of TSLP-activated blood DCs, as compared to freshly purified, Medium-, and TNF-activated DCs. Among TSLP up-regulated genes, we identified molecules associated with skin homing, LC phenotype, and LC function, as determined by a literature-based survey. Conversely, genes not expressed in LCs were not found among TSLP-induced genes. Further experiments showed that TGF-? synergized with TSLP leading to the differentiation of blood BDCA-1+ DCs into bona fide Birbeck granule-positive LCs. Dendritic cells (DC) were purified from the blood of healthy human donors. Each replicate comes from a different donor. There are 6 freshly purified samples (Control_0h), 4 DC samples cultured during 6h with no additional stimulus than the medium (Control_6h), 5 samples cultured during 6h with recombinant TSLP (Thymic Stromal Lymphopoietin at 20 ng/uL) (TSLP_6h) and 3 samples cultured during 6h with recombinant TNF (Tumor necrosis factor at 20 ng/mL) (TNF_6h).

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Gene expression profiling of CD45+CD3-CD11b+MHCII+ subsets in P5 (day 5 after birth) and 1.5M (1.5 months after birth) mouse epidermal cells

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