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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 [RNA-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 | GSE247874 | GEO

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

2024-09-08 | GSE247878 | GEO

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

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

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

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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

Senescent Langerhans cell histiocytosis cells arise from both dendritic cell (DC) and monocyte/DC3 lineages

Project description:Langerhans cell histiocytosis (LCH) is a potentially fatal myeloid neoplasia, stemming from the mononuclear phagocyte (MNP) system. Discrimination of neoplastic cells that share features with normal MNPs is essential for mapping disease origin and pathogenesis. Here, we performed a deep profiling of LCH cells combining single cell RNA-seq and protein analysis enabling us to assess their heterogeneity and compare to their normal counterparts within the tumor microenvironment. Downstream analysis revealed LCH signatures pointing to senescence and tumor immune surveillance escape mechanisms. Developmentally, two major LCH arms, phenotypically resembling DC2 and monocyte/DC3 lineages, were identified and validated in situ across different pathological tissue sites using high-throughput microscopy. The present results support a dual origin model of LCH with an underlying neoplastic hit prior to the fate commitment to DC2 and monocyte/DC3 lineages, and provides basis for development of future targets in LCH and other histiocytic disorders.

2022-12-09 | GSE173923 | GEO

Murine GMP- and MDP-derived classical monocytes have distinct functions and fates [dataset 2]

Project description:Monocytes are short-lived myeloid immune cells that arise from adult hematopoiesis and circulate for a short time in the blood. They comprise two main subsets, in mice defined as classical Ly6Chigh and non-classical Ly6Clow monocytes (CM, NCM). Recent fate mapping and transcriptomic analyses revealed that CM themselves are heterogeneous. Here, we report surface markers that allow segregation of murine GMP- and MDP-derived CM in the BM and blood. Functional characterization, including fate definition following adoptive cell transfer, established that GMP-Mo and MDP-Mo could equal rise to homeostatic CM progeny, such as NCM in blood and gut macrophages, but differentially seeded selected other tissues. Specifically, GMP-Mo and MDP-Mo gave rise to distinct interstitial lung macrophages, thus linking CM dichotomy to previously reported pulmonary macrophage heterogeneity. Collectively, we provide comprehensive evidence for the existence of two functionally distinct CM subsets in the mouse, which differentially contribute to peripheral tissue macrophage populations in homeostasis and following challenge. Our findings are indicative of impact of monocyte ontogeny on in situ differentiation.

2024-05-04 | GSE261594 | GEO

MDP- and Pam3CSK4-induced genes in naïve and tolerant macrophages

Project description:Most of the genes were self-tolerized by Pam3CSK4 and MDP but there was no or minimal cross-tolerization. The transcriptome induced via Nod2 stimulation is greatly expanded in TLR2-tolerant macrophages. Keywords: self and cross tolerance by MDP or Pam3CSK4

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