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

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

PROVIDER: PRJNA1055091 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27307100_1.fastq.gz	Fastqsanger.gz
	SRR27307100_2.fastq.gz	Fastqsanger.gz
	SRR27307101_1.fastq.gz	Fastqsanger.gz
	SRR27307101_2.fastq.gz	Fastqsanger.gz
	SRR27307102_1.fastq.gz	Fastqsanger.gz

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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we show that embryo-derived (e)LCs in newborns retain transcriptional evidence of their macrophage origin, but this is superseded by distinct DC-like immune modules after expansion of the eLC network.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

2025-04-03 | GSE251705 | GEO

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

Project description:Langerhans cells (LCs) are distinct among phagocytes, functioning both as embryo-derived, tissue-resident macrophages in skin innervation and repair and as migrating professional antigen-presenting cells, a function classically assigned to dendritic cells (DCs). Here, we demonstrate that both intrinsic and extrinsic factors imprint this dual identity. Using ablation of embryo-derived LCs in the murine adult skin and tracking differentiation of incoming monocyte-derived replacements, we found intrinsic intraepidermal heterogeneity. We observed that ontogenically distinct monocytes give rise to LCs. Within the epidermis, Jagged-dependent activation of Notch signaling, likely within the hair follicle niche, provided an initial site of LC commitment before metabolic adaptation and survival of monocyte-derived LCs. In the human skin, embryo-derived LCs in newborns retained transcriptional evidence of their macrophage origin, but this was superseded by DC-like immune modules after postnatal expansion. Thus, adaptation to adult skin niches replicates conditioning of LC at birth, permitting repair of the embryo-derived LC network.

| S-EPMC7616733 | biostudies-literature

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

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

| PRJNA1040853 | ENA

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]

2024-09-08 | GSE247874 | GEO

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]

| PRJNA1040849 | ENA

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]

| PRJNA1040858 | ENA

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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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).

2025-05-30 | GSE291916 | GEO

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

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