Shen, Sophie and Werner, Tessa and Lukowski, Samuel W. and Andersen, Stacey and Sun, Yuliangzi and Shim, Woo Jun and Mizikovsky, Dalia and Kobayashi, Sakurako and Outhwaite, Jennifer and Chiu, Han Sheng and Chen, Xiaoli and Chapman, Gavin and Martin, Ella M. M. A. and Xia, Di and Pham, Duy and Su, Zezhuo and Kim, Daniel and Yang, Pengyi and Tan, Men Chee and Sinniah, Enakshi and Zhao, Qiongyi and Negi, Sumedha and Redd, Meredith A. and Powell, Joseph E. and Dunwoodie, Sally L. and Tam, Patrick P. L. and Bodén, Mikael and Ho, Joshua W. K. and Nguyen, Quan and Palpant, Nathan J. (2025) Atlas of multilineage stem cell differentiation reveals TMEM88 as a developmental regulator of blood pressure. Nature Communications, 16 (1). ISSN 2041-1723
Full text not available from this repository.Abstract
Abstract
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 lineages influencing cardiovascular and anthropometric traits. Genetic TMEM88 loss of function models show impaired differentiation of endodermal and mesodermal derivatives in vitro and dysregulated arterial blood pressure in vivo. Together, this study provides an atlas of multilineage stem cell differentiation and analysis pipelines to dissect genetic determinants of mammalian developmental physiology.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 05 May 2025 05:58 |
| Last Modified: | 05 May 2025 05:58 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/1672 |
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