Atlas of multilineage stem cell differentiation reveals TMEM88 as a developmental regulator of blood pressure
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-d...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56533-2 |
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| author | Sophie Shen Tessa Werner Samuel W. Lukowski Stacey Andersen Yuliangzi Sun Woo Jun Shim Dalia Mizikovsky Sakurako Kobayashi Jennifer Outhwaite Han Sheng Chiu Xiaoli Chen Gavin Chapman Ella M. M. A. Martin Di Xia Duy Pham Zezhuo Su Daniel Kim Pengyi Yang Men Chee Tan Enakshi Sinniah Qiongyi Zhao Sumedha Negi Meredith A. Redd Joseph E. Powell Sally L. Dunwoodie Patrick P. L. Tam Mikael Bodén Joshua W. K. Ho Quan Nguyen Nathan J. Palpant |
| author_facet | Sophie Shen Tessa Werner Samuel W. Lukowski Stacey Andersen Yuliangzi Sun Woo Jun Shim Dalia Mizikovsky Sakurako Kobayashi Jennifer Outhwaite Han Sheng Chiu Xiaoli Chen Gavin Chapman Ella M. M. A. Martin Di Xia Duy Pham Zezhuo Su Daniel Kim Pengyi Yang Men Chee Tan Enakshi Sinniah Qiongyi Zhao Sumedha Negi Meredith A. Redd Joseph E. Powell Sally L. Dunwoodie Patrick P. L. Tam Mikael Bodén Joshua W. K. Ho Quan Nguyen Nathan J. Palpant |
| author_sort | Sophie Shen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-058a43f678964a8fb56af1a18ed77a62 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-058a43f678964a8fb56af1a18ed77a622025-02-09T12:44:34ZengNature PortfolioNature Communications2041-17232025-02-0116111910.1038/s41467-025-56533-2Atlas of multilineage stem cell differentiation reveals TMEM88 as a developmental regulator of blood pressureSophie Shen0Tessa Werner1Samuel W. Lukowski2Stacey Andersen3Yuliangzi Sun4Woo Jun Shim5Dalia Mizikovsky6Sakurako Kobayashi7Jennifer Outhwaite8Han Sheng Chiu9Xiaoli Chen10Gavin Chapman11Ella M. M. A. Martin12Di Xia13Duy Pham14Zezhuo Su15Daniel Kim16Pengyi Yang17Men Chee Tan18Enakshi Sinniah19Qiongyi Zhao20Sumedha Negi21Meredith A. Redd22Joseph E. Powell23Sally L. Dunwoodie24Patrick P. L. Tam25Mikael Bodén26Joshua W. K. Ho27Quan Nguyen28Nathan J. Palpant29Institute for Molecular Bioscience, The University of QueenslandInstitute for Molecular Bioscience, The University of QueenslandInstitute for Molecular Bioscience, The University of QueenslandInstitute for Molecular Bioscience, The University of QueenslandInstitute for Molecular Bioscience, The University of QueenslandInstitute for Molecular Bioscience, The University of QueenslandInstitute for Molecular Bioscience, The University of QueenslandInstitute for Molecular Bioscience, The University of QueenslandInstitute for Molecular Bioscience, The University of QueenslandInstitute for Molecular Bioscience, The University of QueenslandInstitute for Molecular Bioscience, The University of QueenslandVictor Chang Cardiac Research InstituteVictor Chang Cardiac Research InstituteInstitute for Molecular Bioscience, The University of QueenslandInstitute for Molecular Bioscience, The University of QueenslandSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, PokfulamComputational Systems Biology Group, Children’s Medical Research Institute, University of SydneyComputational Systems Biology Group, Children’s Medical Research Institute, University of SydneyInstitute for Molecular Bioscience, The University of QueenslandInstitute for Molecular Bioscience, The University of QueenslandInstitute for Molecular Bioscience, The University of QueenslandInstitute for Molecular Bioscience, The University of QueenslandInstitute for Molecular Bioscience, The University of QueenslandGarvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical ResearchVictor Chang Cardiac Research InstituteEmbryology Research Unit, Children’s Medical Research Institute, University of SydneySchool of Chemistry and Molecular Biosciences, The University of QueenslandSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, PokfulamInstitute for Molecular Bioscience, The University of QueenslandInstitute for Molecular Bioscience, The University of QueenslandAbstract 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.https://doi.org/10.1038/s41467-025-56533-2 |
| spellingShingle | Sophie Shen Tessa Werner Samuel W. Lukowski Stacey Andersen Yuliangzi Sun Woo Jun Shim Dalia Mizikovsky Sakurako Kobayashi Jennifer Outhwaite Han Sheng Chiu Xiaoli Chen Gavin Chapman Ella M. M. A. Martin Di Xia Duy Pham Zezhuo Su Daniel Kim Pengyi Yang Men Chee Tan Enakshi Sinniah Qiongyi Zhao Sumedha Negi Meredith A. Redd Joseph E. Powell Sally L. Dunwoodie Patrick P. L. Tam Mikael Bodén Joshua W. K. Ho Quan Nguyen Nathan J. Palpant Atlas of multilineage stem cell differentiation reveals TMEM88 as a developmental regulator of blood pressure Nature Communications |
| title | Atlas of multilineage stem cell differentiation reveals TMEM88 as a developmental regulator of blood pressure |
| title_full | Atlas of multilineage stem cell differentiation reveals TMEM88 as a developmental regulator of blood pressure |
| title_fullStr | Atlas of multilineage stem cell differentiation reveals TMEM88 as a developmental regulator of blood pressure |
| title_full_unstemmed | Atlas of multilineage stem cell differentiation reveals TMEM88 as a developmental regulator of blood pressure |
| title_short | Atlas of multilineage stem cell differentiation reveals TMEM88 as a developmental regulator of blood pressure |
| title_sort | atlas of multilineage stem cell differentiation reveals tmem88 as a developmental regulator of blood pressure |
| url | https://doi.org/10.1038/s41467-025-56533-2 |
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