Biology subjects

Gopee, N. H.

Publications and source records attributed to Gopee, N. H..

5 recordsLinked to original sources

bioRxiv2026

Function-driven geometry directs human pilosebaceous unit development

Single-cell technologies have generated cell censuses of tissues, however, how tissue geometry reflects functional needs remains poorly characterized. The human pilosebaceous unit offers a tractable model, a prenatally-formed complex mini-organ combining hair and sebum production with a stem cell reservoir. Using histomorphology, spatial transcriptomics, and single-cell multiomics on the same human prenatal scalp skin samples (8-19 post-conception weeks), integrated and analyzed using machine learning approaches, we built a spatiotemporal map of pilosebaceous unit development. We demonstrate that epithelial-mesenchymal interactions coordinate cellular fate and organogenesis, using an in vitro hair-bearing skin organoid model to validate this tissue-patterning. In addition, we show sebaceous gland developmental programmes are overcome during tumor formation. Our large-scale multi-modal analysis provides a unique framework for understanding form and function of tissues with applications in tissue engineering and pathology.

developmental biology↗

bioRxiv2026

Hidden immune memory niches in inflammatory skin diseases

Disease-associated histopathological features are widely used to identify tissue microenvironments or niches for diagnostics and treatment response in clinical practice. However, despite its widespread use, histopathology does not reveal the full cellular and molecular composition of known pathological niches. Furthermore, the existence of pathological niches that may not be histologically discernible remains unknown. In this study, we generated a spatially-resolved multi-modal molecular atlas of [~]5 million human skin cells (including 113 skin sections profiled using Xenium-5k) and applied deep learning to unbiasedly decode 26 skin niches in health and disease. Several disease-associated niches corresponded to known histopathological features, and we defined their cellular and molecular features, co-localisations, and interactions. Additionally, we discovered an immunologically active role for skin appendageal structures in disease mechanisms, potentially contributing to inflammatory memory, that was not identifiable using standard histopathological analysis. These include a resident memory T cell-rich niche in the sebaceous gland and a plasma cell-rich niche in the sweat gland, analogous to the gland-associated immune niche in lung. Finally, we illustrate how our atlas can be used to generate high-resolution representations using transfer learning, resolving rare T cell and sebocyte subsets not possible in the original studies, validating niche identification, and the spatial enrichment of candidate genes linked to disease-associated genetic variants. Overall, our study links histopathology and atlas-scale genomics to reveal novel insights into inflammatory disease pathogenesis, chronicity, and potentially curative therapeutic avenues, using skin as an exemplar tissue for this approach.

immunology↗

bioRxiv2024

A single cell and spatial genomics atlas of human skin fibroblasts in health and disease

Fibroblasts are critical cells that shape the architecture and cellular ecosystems in multiple tissues. Understanding fibroblast heterogeneity and their spatial context in health and disease has enormous clinical relevance. In this study, we constructed a spatially-resolved atlas of human skin fibroblasts from healthy skin and 23 skin disorders. We define 6 major skin fibroblast populations in health and a further three skin disease-specific fibroblast subtypes, and demonstrate the fibroblast composition in different types of skin disease. We characterise a human-specific fibroblastic reticular cell (FRC)-like subtype in the skin perivascular niche and postulate their origin from prenatal skin lymphoid tissue organiser (LTo)-like cells. We also show that inflammatory myofibroblasts (IL11+MMP1+CXCL5+IL7R+) are a conserved fibroblast subtype in inflammatory disorders and cancers across multiple human tissues. We provide a harmonised nomenclature for skin fibroblasts that integrates previous findings from human skin and other tissues.

cell biology↗

bioRxiv2024

Spatiotemporal Single-Cell Roadmap of Human Skin Wound Healing

Wound healing is vital for human health, yet the details of cellular dynamics and coordination in human wound repair remain largely unexplored. To address this, we conducted single-cell and spatial transcriptomics analyses on human skin and acute wound tissues through inflammation, proliferation, and remodeling phases of wound repair from the same individuals, monitoring the cellular and molecular dynamics of human skin wound healing at an unprecedented spatiotemporal resolution. This singular roadmap reveals the cellular architecture of the wound margin and identifies FOSL1 as a critical driver of re-epithelialization. It shows that pro-inflammatory macrophages and fibroblasts sequentially support keratinocyte migration like a relay race across different healing stages. Comparison with single-cell data from venous and diabetic foot ulcers uncovers a link between failed keratinocyte migration and impaired inflammatory response in chronic wounds. Additionally, comparing human and mouse acute wound transcriptomes underscores the indispensable value of this roadmap in bridging basic research with clinical innovations. HighlightsO_LIA spatiotemporal atlas to explore human in vivo gene expression across wound healing C_LIO_LIWound margin architecture unveils a model for human re-epithelialization C_LIO_LIDistinct healing challenges in venous ulcers and diabetic foot ulcers C_LIO_LIUnique human healing traits emerge in cellular heterogeneity and gene expression C_LI

cell biology↗

bioRxiv2023

A human prenatal skin cell atlas reveals immune cell regulation of skin morphogenesis

Human prenatal skin is populated by innate immune cells including macrophages, and whether they act solely in immunity or have additional functions in morphogenesis is unclear. We assembled the first comprehensive multi-omic reference atlas of prenatal human skin (7-16 post-conception weeks), combining single cell and spatial transcriptomic data, to characterise the skins microenvironmental cellular organisation. This revealed that crosstalk between non-immune and immune cells underpins formation of hair follicles, has implications for scarless wound healing, and is critical for skin angiogenesis. We benchmarked a skin organoid model, derived from human embryonic stem (ES) and induced pluripotent stem (iPS) cells, against prenatal and adult skin, demonstrating close recapitulation of the epidermal and dermal skin components during hair follicle development. Notably, the skin organoid lacked immune cells and had markedly diminished endothelial cell heterogeneity and quantity. From our in vivo skin cell atlas data, we found that macrophages and macrophage-derived growth factors play a key role in driving endothelial development prenatally. Indeed, vascular network formation was enhanced following transfer of autologous iPS-derived macrophages into both endothelial cell angiogenesis assays and skin organoid cultures. In summary, innate immune cells moonlight as key players in skin morphogenesis beyond their conventional immune roles, a function they achieve via extensive crosstalk with non-immune cells. Finally, we leveraged our human prenatal skin cell atlas to further our understanding of the pathogenesis of genetic hair and skin disorders.

developmental biology↗