Biology subjects

Goss, G.

Publications and source records attributed to Goss, G..

4 recordsLinked to original sources

bioRxiv2025

Mesodermal-niche interactions direct specification and differentiation of pancreatic islet cells in human multilineage organoids

Tissues develop and function within a highly complex microenvironment, where diverse cell types interact in tightly regulated spatial and temporal patterns1,2. Through distinct, relay-like waves of activity, these cells collectively shape tissue formation, ensuring that each component emerges in the right place at the right time1,2. Such coordinated cues establish the structural and biochemical framework that drives cell differentiation and tissue organization. Accurately modelling this process in humans requires the development of complex multicellular systems. Here, we pair spatial transcriptomics of the human foetal pancreas with an induced pluripotent stem cell (iPSC)-based multilineage model that faithfully recapitulate the complex, hierarchical processes underlying human pancreatic islet formation. We show that iPSC-derived pancreatic mesodermal lineages direct endocrine commitment from pancreatic progenitors, by suppressing off-target fates and orchestrating niche-mediated spatio-temporal cues that promote beta-cell differentiation. Our results identify a vascular-rich niche, featuring pancreatic pericytes, which is associated with a neural repulsion program and may contribute to shaping the islet microenvironment. We benchmark our in vitro multilineage organoid system against spatial transcriptomics of the human foetal pancreas. Together, these findings identify the key cellular actors and contact-dependent mechanisms that build the human endocrine pancreas, providing a critical model for studying human islet development and disease.

developmental biology↗

bioRxiv2025

Spatially organized cellular communities shape functional tissue architecture in the pancreas

Organ function depends on the precise spatial organization of cells across multiple scales, from individual cells to cellular communities that form specialized local niches and, ultimately, complex higher-order structures. While the identities of individual cell are increasingly well-defined, our understanding of how these diverse cell types are spatially distributed and communicate remains incomplete. In this study, we combine single-cell and spatial transcriptomic analyses to map pancreatic cell populations across space and time, from embryonic development to adult homeostasis in mice. Using these comprehensive maps, we systematically resolve spatial heterogeneity among pancreatic cell types and uncover basic tissue niches, which emerge as epithelial-mesenchymal units. We further characterize these niches functionally in both mouse and human models. We demonstrate that the mesenchymal lineage initially diversifies into various subtypes with specialized supportive roles during embryonic development. However, this complexity gradually diminishes over time, ultimately converging into a limited number of fibroblast sub-types in adult tissue. Our findings shed light on how different progenitor lineages co-develop and organize into structured communities that establish a mature, functional pancreas. This foundational framework could inform strategies for in vitro organogenesis and tissue-engineering in the context of pancreatic diseases.

developmental biology↗

bioRxiv2022

Improving stem cell-derived pancreatic islets using single-cell multiome-inferred regulomes

Pancreatic islet cells derived from human pluripotent stem cells hold great promise for modeling and treating diabetes. Differences between stem cell-derived and primary islets remain, but molecular insights to inform improvements are limited. Here, we acquire single-cell transcriptomes and accessible chromatin profiles during in vitro islet differentiation and pancreas from childhood and adult donors for comparison. We delineate major cell types, define their regulomes, and describe spatiotemporal gene regulatory relationships between transcription factors. CDX2 emerged as a regulator of enterochromaffin-like cells, which we show resemble a transient, previously unrecognized, CDX2+ pre-{beta}-cell population in fetal pancreas, arguing against a proposed non-pancreatic origin. Furthermore, we observe insufficient activation of signal-dependent transcriptional programs during in vitro {beta}-cell maturation and identify sex hormones as drivers of {beta}-cell proliferation in childhood. Altogether, our analysis provides a comprehensive understanding of cell fate acquisition in stem cell-derived islets and a framework for manipulating cell identities and maturity.

cell biology↗

bioRxiv2021

Role of distinct fibroblast lineages and immune cells in dermal repair following UV radiation induced tissue damage

Solar ultraviolet radiation (UVR) is a major source of skin damage, resulting in inflammation, premature ageing and cancer. While several UVR-induced changes, including extracellular matrix reorganisation and epidermal DNA damage, have been documented, the role of different fibroblast lineages and their communication with immune cells has not been explored. We show that acute and chronic UVR exposure led to selective loss of fibroblasts from the upper dermis in human and mouse skin. Lineage tracing and in vivo live imaging revealed that repair following acute UVR is predominantly mediated by papillary fibroblast proliferation and migration. In contrast, chronic UVR exposure led to a permanent loss of papillary fibroblasts, with expansion of fibroblast membrane protrusions partially compensating for the reduction in cell number. Although UVR strongly activated Wnt-signalling in skin, stimulation of fibroblast proliferation by epidermal {beta}-catenin stabilisation did not support papillary dermis repair. Acute UVR triggered an infiltrate of neutrophils and T cell subpopulations and increased pro-inflammatory prostaglandin signalling in skin. Depletion of CD4 and CD8 positive cells resulted in increased papillary fibroblast depletion, which correlated with an increase in DNA damage and reduction in fibroblast proliferation. Conversely, topical COX-2 inhibition prevented fibroblast depletion and neutrophil infiltration after UVR. We conclude that loss of papillary fibroblasts is primarily induced by a deregulated inflammatory response, with infiltrating T cells supporting fibroblast survival upon UVR-induced environmental stress. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=91 SRC="FIGDIR/small/447606v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@d246bborg.highwire.dtl.DTLVardef@121b5faorg.highwire.dtl.DTLVardef@324114org.highwire.dtl.DTLVardef@14e9eb7_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗