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Convergent evolution of MDP-monocyte differentiation in adult skin permits repair of the Langerhans cell network

ABSTRACT: Convergent evolution of MDP-monocyte differentiation in adult skin permits repair of the Langerhans cell network

PROVIDER: PRJNA1040853 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26842400_1.fastq.gz	Fastqsanger.gz
	SRR26842400_2.fastq.gz	Fastqsanger.gz
	SRR26842401_1.fastq.gz	Fastqsanger.gz
	SRR26842401_2.fastq.gz	Fastqsanger.gz
	SRR26842402_1.fastq.gz	Fastqsanger.gz

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Convergent evolution of MDP-monocyte differentiation in adult skin permits repair of the Langerhans cell network [RNA-seq]

Project description:Convergent evolution of MDP-monocyte differentiation in adult skin permits repair of the Langerhans cell network [RNA-seq]

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Convergent evolution of MDP-monocyte differentiation in adult skin permits repair of the Langerhans cell network [scRNA-seq]

Project description:Convergent evolution of MDP-monocyte differentiation in adult skin permits repair of the Langerhans cell network [scRNA-seq]

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Convergent evolution of MDP-monocyte differentiation in adult skin permits repair of the Langerhans cell network [scRNA-seq]

Project description:Langerhans cells (LCs) are a unique population of phagocytes programmed within embryonic skin to maintain tissue and immunological homeostasis at the epidermal barrier site. Unique amongst tissue-resident macrophages, LCs play roles in skin innervation and repair, while also functioning as migrating professional antigen presenting cells, a capability classically assigned to dendritic cells (DC). We current lack insight into the molecular pathways that determine this dichotomy, when they are established, and whether precursors recruited to the adult skin niche access the same instructive signals laid down in utero. Tracking differentiation of monocyte-derived (m)LCs after destruction of embryo-derived cells in murine adult skin, revealed intrinsic intra-epidermal heterogeneity and selection of MDP-monocytes to by-pass gene programmes specifying a macrophage fate. Adopting a process unique to adult skin, subsequent extrinsic specification of EpCAM+ precursors via follicular Notch ligands, and aryl hydrocarbon receptor (Ahr) signalling, combined to determine commitment to resident mLCs. Using a unique human LC dataset, we demonstrated that embryo-derived (e)LCs in newborn human skin retained transcriptional evidence of their macrophage origin, which was superseded by a distinct DC-like immune modules following proliferation in infant skin. Thus, convergent differentiation of monocytes within adult skin exploits novel molecular pathways to replicate conditioning of eLC towards more immunogenic DC-like cells within post-natal skin.

2024-09-08 | GSE247878 | GEO

Convergent evolution of MDP-monocyte differentiation in adult skin permits repair of the Langerhans cell network [RNA-seq]

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Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity

Project description:Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity

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Convergent evolution of MDP-monocyte differentiation in adult skin permits repair of the Langerhans cell network

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-09-08 | GSE247879 | GEO

Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity

Project description:Langerhans cells (LCs) maintain tissue and immunological homeostasis at the epidermal barrier site. They are unique among phagocytes in functioning both as embryo-derived, tissue-resident macrophages that influence skin innervation and repair, and as migrating professional antigen presenting cells, a capability classically assigned to dendritic cells (DC). Here we report the mechanisms that determine this dual identity. Using ablation of embryo-derived LCs in murine adult skin and tracked differentiation of incoming monocyte-derived replacements, we reveal intrinsic intra-epidermal heterogeneity. Macrophage-dendritic cell precursors are selected for survival in the skin environment, by-passing gene programs that specify a macrophage fate. We demonstrate that the hair follicle niche provides Notch signals that impose LC identity. In human skin, we show that embryo-derived (e)LCs in newborns retain transcriptional evidence of their macrophage origin, but this is superseded by distinct DC-like immune modules after expansion of the eLC network. Thus, cellular adaptation to the adult skin niche replicates conditioning of eLC, instructing DC-like programmes within macrophages

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Project description:Trancriptomics of primary human monocytes, Langerhans cells (LC), and monocyte-derived Langerhans cells (moLC)

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Natriuretic Peptides Modulate Monocyte-Derived Langerhans Cell Differentiation and Promote a Migratory Phenotype

Project description:Introduction: The interaction between the nervous and immune systems is crucial for maintaining homeostasis and can influence disease progression in inflammatory skin diseases, such as atopic dermatitis (AD). Sensory neurons in the skin can secrete neuropeptides that modulate immune cell activity, including Langerhans cells (LCs), the primary antigen-presenting cells in the epidermis. This study investigates the effects of neuropeptides on the differentiation of monocyte-derived LCs (moLCs), specifically the neuropeptides with the most profound effect, i.e. atrial- and B-type natriuretic peptides (ANP and BNP, respectively).

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MDP phosphorylation by NAGK is essential for NOD2 activation

Project description:Bacterial cell wall components provide various unique molecular structures that are detected by pattern recognition receptors (PRRs) of the innate immune system as non-self. Most bacterial species form a cell wall that consists of peptidoglycan, a polymeric structure comprising of alternating amino sugars. Muramyl dipeptide (MDP) is the minimal, biologically active molecular structure derived from peptidoglycan, and its immunogenicity is well documented in numerous studies. MDP is sensed by the cytosolic nucleotide-binding and nucleotide oligomerization domain-like receptor 2 (NOD2), which triggers a pro-inflammatory response upon engagement 1,2. Conducting a forward genetic screen to identify factors required for MDP detection, we discovered that N-acetylglucosamine kinase (NAGK) is essential for the immunostimulatory activity of MDP. NAGK, which has previously been identified to contribute to the hexosamine salvage pathway in humans, is broadly expressed and inducible in innate immune cells. Mechanistically, NAGK functions upstream of NOD2 in that it directly phosphorylates the N-acetylmuramic moiety of MDP at the hydroxyl group of its C6 position, yielding 6-O-phospho-MDP. NAGK-phosphorylated MDP constitutes an essential component of NOD2 dependent signal transduction. Altogether, these results unveil a previously unknown interconnection of amino sugar metabolism and innate immunity to bacterial cell walls.

2022-06-13 | PXD022384 | Pride

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