Fate and State Transitions during Human Blood Vessel Organoid Development: Time Course
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PROVIDER: PRJEB85545 | ENA |
REPOSITORIES: ENA
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Project description:Fate and State Transitions during Human Blood Vessel Organoid Development: Perturbation
| PRJEB85862 | ENA
Project description:Human blood vessel organoids (hBVOs) derived from human pluripotent stem cells have emerged as a novel system to understand human vascular development, model disorders, and develop regenerative therapies. However, it was unclear which molecular states constitute hBVOs and how cells differentiate and self-organize within hBVOs in vitro and after transplantation. Here we reconstruct hBVO development over a time course using single-cell transcriptomics. Data includes day 3, 4, 5, 6, 7, 14 and 21 of hBVO differentiation, as well as 2 months post-transplantation of 14-day hBVOs into immunocompromised mice. We observe progenitor states that bifurcate into endothelial and mural fates, and find that hBVOs do not acquire definitive arterio-venous endothelial identities in vitro. Chromatin accessibility profiling at days 3, 4 and 7 identifies gene regulatory network (GRN) features associated with endothelial and mural fate decisions. Transcriptome-coupled lineage recording reveals multipotent progenitor states within BVOs. These data provide the first comprehensive cell state atlas of BVO development.
2025-03-21 | E-MTAB-14807 | biostudies-arrayexpress
Project description:Human blood vessel organoids (hBVOs) have emerged as a system to model human vascular development and disease. Here, we use genetic and signaling pathway perturbations to reconstruct hBVO development. We use single-cell genetic perturbations to identify transcription factors (TFs) and receptors involved in cell fate specification, including a role for MECOM in endothelial and mural specification. We assess the potential of BVOs to generate organotypic states, particularly brain vasculature-specificity, using small-molecule and TF-gene over expression perturbation. Finally, we mimic inflammatory and diabetic conditions in hBVOs in vitro. Altogether, we provide data for the first comprehensive cell state atlas of hBVO development and illuminate the power and limitation of hBVOs for translational research.
2025-03-01 | E-MTAB-14839 | biostudies-arrayexpress
Project description:identified vessel derived protein promote cardiac organoid compaction maturation
2025-06-16 | PXD065083 |
Project description:Acquisition of specific cell shapes and morphologies is a central component of cell fate transitions. Although the signaling circuits and gene regulatory networks regulating pluripotent stem cell differentiation have been intensely studied, how these networks are integrated in space and time with morphological transitions and mechanical deformations that occur during state transitions remains a fundamental open question. Here, we discover that stem cell fate transitions are gated by two critical signals - nuclear envelope fluctuations and osmotic stress - that emanate from growth factor signaling-controlled changes in nuclear volume and nucleoplasm viscosity/density to subsequently trigger changes in nuclear architecture and transcription. We observe that fate transitions in the early human embryo and in an in vitro pluripotency exit model are guided by rapid changes in nuclear volume and nuclear envelope mechanics. These changes alter nuclear mechanosensitivity and trigger changes in nucleoplasmic viscosity and nuclear condensates that together prime chromatin for a cell fate transition. However, while this mechanical priming accelerates fate transitions, sustained biochemical signals are required for robust induction of differentiation. Our findings uncover a critical mechanochemical feedback mechanism that integrates nuclear mechanics, shape and volume with biochemical signaling and chromatin state to control cell fate transition dynamics.
2025-07-21 | GSE268087 | GEO
Project description:Acquisition of specific cell shapes and morphologies is a central component of cell fate transitions. Although the signaling circuits and gene regulatory networks regulating pluripotent stem cell differentiation have been intensely studied, how these networks are integrated in space and time with morphological transitions and mechanical deformations that occur during state transitions remains a fundamental open question. Here, we discover that stem cell fate transitions are gated by two critical signals - nuclear envelope fluctuations and osmotic stress - that emanate from growth factor signaling-controlled changes in nuclear volume and nucleoplasm viscosity/density to subsequently trigger changes in nuclear architecture and transcription. We observe that fate transitions in the early human embryo and in an in vitro pluripotency exit model are guided by rapid changes in nuclear volume and nuclear envelope mechanics. These changes alter nuclear mechanosensitivity and trigger changes in nucleoplasmic viscosity and nuclear condensates that together prime chromatin for a cell fate transition. However, while this mechanical priming accelerates fate transitions, sustained biochemical signals are required for robust induction of differentiation. Our findings uncover a critical mechanochemical feedback mechanism that integrates nuclear mechanics, shape and volume with biochemical signaling and chromatin state to control cell fate transition dynamics.
2025-07-21 | GSE268086 | GEO
Project description:Acquisition of specific cell shapes and morphologies is a central component of cell fate transitions. Although the signaling circuits and gene regulatory networks regulating pluripotent stem cell differentiation have been intensely studied, how these networks are integrated in space and time with morphological transitions and mechanical deformations that occur during state transitions remains a fundamental open question. Here, we discover that stem cell fate transitions are gated by two critical signals - nuclear envelope fluctuations and osmotic stress - that emanate from growth factor signaling-controlled changes in nuclear volume and nucleoplasm viscosity/density to subsequently trigger changes in nuclear architecture and transcription. We observe that fate transitions in the early human embryo and in an in vitro pluripotency exit model are guided by rapid changes in nuclear volume and nuclear envelope mechanics. These changes alter nuclear mechanosensitivity and trigger changes in nucleoplasmic viscosity and nuclear condensates that together prime chromatin for a cell fate transition. However, while this mechanical priming accelerates fate transitions, sustained biochemical signals are required for robust induction of differentiation. Our findings uncover a critical mechanochemical feedback mechanism that integrates nuclear mechanics, shape and volume with biochemical signaling and chromatin state to control cell fate transition dynamics.
2025-07-21 | GSE268084 | GEO
Project description:Acquisition of specific cell shapes and morphologies is a central component of cell fate transitions. Although the signaling circuits and gene regulatory networks regulating pluripotent stem cell differentiation have been intensely studied, how these networks are integrated in space and time with morphological transitions and mechanical deformations that occur during state transitions remains a fundamental open question. Here, we discover that stem cell fate transitions are gated by two critical signals - nuclear envelope fluctuations and osmotic stress - that emanate from growth factor signaling-controlled changes in nuclear volume and nucleoplasm viscosity/density to subsequently trigger changes in nuclear architecture and transcription. We observe that fate transitions in the early human embryo and in an in vitro pluripotency exit model are guided by rapid changes in nuclear volume and nuclear envelope mechanics. These changes alter nuclear mechanosensitivity and trigger changes in nucleoplasmic viscosity and nuclear condensates that together prime chromatin for a cell fate transition. However, while this mechanical priming accelerates fate transitions, sustained biochemical signals are required for robust induction of differentiation. Our findings uncover a critical mechanochemical feedback mechanism that integrates nuclear mechanics, shape and volume with biochemical signaling and chromatin state to control cell fate transition dynamics.
2025-07-21 | GSE267743 | GEO
Project description:Acquisition of specific cell shapes and morphologies is a central component of cell fate transitions. Although the signaling circuits and gene regulatory networks regulating pluripotent stem cell differentiation have been intensely studied, how these networks are integrated in space and time with morphological transitions and mechanical deformations that occur during state transitions remains a fundamental open question. Here, we discover that stem cell fate transitions are gated by two critical signals - nuclear envelope fluctuations and osmotic stress - that emanate from growth factor signaling-controlled changes in nuclear volume and nucleoplasm viscosity/density to subsequently trigger changes in nuclear architecture and transcription. We observe that fate transitions in the early human embryo and in an in vitro pluripotency exit model are guided by rapid changes in nuclear volume and nuclear envelope mechanics. These changes alter nuclear mechanosensitivity and trigger changes in nucleoplasmic viscosity and nuclear condensates that together prime chromatin for a cell fate transition. However, while this mechanical priming accelerates fate transitions, sustained biochemical signals are required for robust induction of differentiation. Our findings uncover a critical mechanochemical feedback mechanism that integrates nuclear mechanics, shape and volume with biochemical signaling and chromatin state to control cell fate transition dynamics.
2025-07-21 | GSE268085 | GEO
Project description:As an evolutionarily conserved master regulator of metabolism, mechanistic target of rapamycin complex 1 (mTORC1) regulates cell states and fates in development, cancer and aging. mTORC1 activity regulation was critical for pluripotent stem cells maintenance and cell fate transitions. Inhibition of mTORC1 induces embryonic stem cells (ESCs) entry into a paused state which reversibly arrests self-renewal leaving pluripotency intact. Hyperactivation of mTORC1 impedes both pluripotency re-establishment and exit of PSCs. As shown that mTORC1 mediates TFE3 nuclear translocation block pluripotency exit, whether similar mechanisms through transcription factor TFE3 are involved in these processes, and the detailed mechanism by which mTORC1-TFE3 regulates critical transcriptional processes for these transitions, remain unclear. In this study, we demonstrate that the nuclear translocation of TFE3, induced by hyperactivation of mTORC1, results in its binding to the nucleosome remodeling and deacetylation (NuRD) complex in both re-establishment and exit of pluripotency. This interaction inhibits the expression of various crucial genes during different fate transitions of PSCs. Our findings uncover a common and key role of TFE3-NuRD association as mediator of mTORC1 to block pluripotent cell fate transitions, with implications for various fields including physiological and pathological diseases.
2025-07-09 | GSE301743 | GEO