Loss of Fgf9 in mice leads to pancreatic hypoplasia and asplenia

Patzek, Sophie; Liu, Zhe; O, Sean de la; Chang, Sean; Byrnes, Lauren; Zhang, Xiuqin; Ornitz, David M.; Sneddon, Julie B.

doi:10.1016/j.isci.2023.106500

Cited by 2 publications

(1 citation statement)

References 88 publications

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“…The acinar cell cluster GO enrichment of regulation of neuron projection development contains the gene GFI1 , which is known for its function in development of acinar cells 58 . Furthermore, FGF9 and FGF10 , genes recently shown to be involved in pancreatic development 59 and previously known to be important for neuronal development and maturation 60 play a role in the GO pathway developmental growth for the acinar cell cluster. In the endocrine cluster, the GO pathway neuron projection morphogenesis is characterised by Pax6 , a gene responsible for development of the pancreas and other neuroectodermal structures, 61 ISL1 , a gene important for beta cell function, 62 and ITGB1 , a gene coding for an integrin critical for islet cell development in the pancreas 63 and for neuronal cell migration 64 .…”

Section: Resultsmentioning

confidence: 99%

Analysis of single nuclear chromatin accessibility reveals unique myeloid populations in human pancreatic ductal adenocarcinoma

Pratt,

Ma,

Dziadowicz

et al. 2024

Clinical & Translational Med

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BackgroundA better understanding of the pancreatic ductal adenocarcinoma (PDAC) immune microenvironment is critical to developing new treatments and improving outcomes. Myeloid cells are of particular importance for PDAC progression; however, the presence of heterogenous subsets with different ontogeny and impact, along with some fluidity between them, (infiltrating monocytes vs. tissue‐resident macrophages; M1 vs. M2) makes characterisation of myeloid populations challenging. Recent advances in single cell sequencing technology provide tools for characterisation of immune cell infiltrates, and open chromatin provides source and function data for myeloid cells to assist in more comprehensive characterisation. Thus, we explore single nuclear assay for transposase accessible chromatin (ATAC) sequencing (snATAC‐Seq), a method to analyse open gene promoters and transcription factor binding, as an important means for discerning the myeloid composition in human PDAC tumours.MethodsFrozen pancreatic tissues (benign or PDAC) were prepared for snATAC‐Seq using 10× Chromium technology. Signac was used for preliminary analysis, clustering and differentially accessible chromatin region identification. The genes annotated in promoter regions were used for Gene Ontology (GO) enrichment and cell type annotation. Gene signatures were used for survival analysis with The Cancer Genome Atlas (TCGA)‐pancreatic adenocarcinoma (PAAD) dataset.ResultsMyeloid cell transcription factor activities were higher in tumour than benign pancreatic samples, enabling us to further stratify tumour myeloid populations. Subcluster analysis revealed eight distinct myeloid populations. GO enrichment demonstrated unique functions for myeloid populations, including interleukin‐1b signalling (recruited monocytes) and intracellular protein transport (dendritic cells). The identified gene signature for dendritic cells influenced survival (hazard ratio = .63, p = .03) in the TCGA‐PAAD dataset, which was unique to PDAC.ConclusionsThese data suggest snATAC‐Seq as a method for analysis of frozen human pancreatic tissues to distinguish myeloid populations. An improved understanding of myeloid cell heterogeneity and function is important for developing new treatment targets in PDAC.

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