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oai:figshare.com:article/32640435 2026-10-01T16:31:11Z portal_1172 item_type_8 month_year_10_2026

Development of novel models of kidney damage using induced human pluripotent stem cells Grace Todd (24169263) PUREID: 617473784 Gremlin1 GREM1 organoid Kidney BMP BMP antagonist bone morphogenetic protein induced pluripotent stem cells iPSCs transcription factor gene regulation bioinformatics analysis modeling small molecule inhibitor <p>Gremlin 1 is a secreted cystine knot glycoprotein that regulates BMP signalling during development and disease. A bioinformatic approach was used to investigate transcriptional regulation of Grem1. The presence of multiple putative binding sites for steroid hormone transcription factor were identified within the cCREs regions of the Grem1. By datamining a ChIP-seq database containing peer reviewed published data found evidence of peak calling of the transcription factor at the promotor region of GREM1 and<i> Invitro </i>validation showed the BEAS-2B cells treated with a synthetic ligand had significantly reduced GREM1 mRNA expression suggested that GREM1 expression may be regulated by steroid hormone receptors. Organoids are in vitro 3Dmulticellular structures that model primitive in vivo organs. Developing differentiation methods to generate kidney organoid models offer a new perspective to investigate kidney development and disease. A method ford ifferentiating P019 L47, an iPSc cell line derived from mononuclear blood cells to kidney organoids, was generated based on previously published kidney organoid protocols. The kidney organoids were characterised via qPCR, Westernblot, H&E staining and immunofluorescence to confirm the presence of posterior and anterior intermediate mesoderm cell populations and intermediated mesoderm derived architecture. Preliminary work to generate a GREM1 reduced kidney organoid model began by investigated the use of small molecule inhibitors to prevent GREM1 antagonism. Of the compounds tested by luciferase assay small molecule inhibitor 04_A was the only compound to be able to significantly inhibit GREM1 to ‘rescue’ BMP2 signalling. The next step in creating a GREM1 kidney organoid model would involve developing a robust method to measure GREM1 activity within the kidney organoids followed by treating 04_Ato differentiating kidney organoids to investigate GREM1 role during nephrogenesis.</p><p></p> 2026-10-01T16:31:11Z Text Thesis 10.17034/32640435.v1 https://figshare.com/articles/thesis/Development_of_novel_models_of_kidney_damage_using_induced_human_pluripotent_stem_cells/32640435 All Rights Reserved