biostudies-literatureShen SNational Heart Foundation of Australia (Heart Foundation)Department of Education and Training | Australian Research Council (ARC)Department of Health | National Health and Medical Research Council (NHMRC)1356https://www.ebi.ac.uk/biostudies/studies/S-EPMC11794859biostudies-literatureUnknown16(1)Pluripotent stem cells provide a scalable approach to analyse molecular regulation of cell differentiation across developmental lineages. Here, we engineer barcoded induced pluripotent stem cells to generate an atlas of multilineage differentiation from pluripotency, encompassing an eight-day time course with modulation of WNT, BMP, and VEGF signalling pathways. Annotation of in vitro cell types with reference to in vivo development reveals diverse mesendoderm lineage cell types including lateral plate and paraxial mesoderm, neural crest, and primitive gut. Interrogation of temporal and signalling-specific gene expression in this atlas, evaluated against cell type-specific gene expression in human complex trait data highlights the WNT-inhibitor gene TMEM88 as a regulator of mesendodermal lNature communicationsAtlas of multilineage stem cell differentiation reveals TMEM88 as a developmental regulator of blood pressure.PMC117948591110751106721GNT200892819010279311734691143163APP11075992007896Kim DPham DKobayashi SRedd MAMartin EMMAPowell JEPalpant NJTam PPLAndersen SLukowski SWZhao QBoden MShen SChen XSu ZSinniah EXia DChapman GOuthwaite JWerner TNguyen QShim WJChiu HSSun YHo JWKTan MCNegi SDunwoodie SLYang PMizikovsky DfalseAtlas of multilineage stem cell differentiation reveals TMEM88 as a developmental regulator of blood pressure.Pluripotent stem cells provide a scalable approach to analyse molecular regulation of cell differentiation across developmental lineages. Here, we engineer barcoded induced pluripotent stem cells to generate an atlas of multilineage differentiation from pluripotency, encompassing an eight-day time course with modulation of WNT, BMP, and VEGF signalling pathways. Annotation of in vitro cell types with reference to in vivo development reveals diverse mesendoderm lineage cell types including lateral plate and paraxial mesoderm, neural crest, and primitive gut. Interrogation of temporal and signalling-specific gene expression in this atlas, evaluated against cell type-specific gene expression in human complex trait data highlights the WNT-inhibitor gene TMEM88 as a regulator of mesendodermal l2025-01-01T00:00:00Z2025 Feb2026-06-02T02:01:17.183Z2025-04-04T02:09:38.79ZS-EPMC117948593990498010.1038/s41467-025-56533-2