| Project/Area Number |
22K20642
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0701:Biology at molecular to cellular levels, and related fields
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Vadivelu Raja Kumar 国立研究開発法人理化学研究所, 開拓研究本部, 基礎科学特別研究員 (60963543)
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| Project Period (FY) |
2022-08-31 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | Cryogel / Mechanical Constraint / iPSCs / Axial convergence / Germ layers / Neural fate / Neuromesodermal / hIPSCs / Mechanobiology / Gastruloid / Axial patterning / Neural Induction / Neuromesoderm / organogenesis / pluripotent / Embryonic Organoid |
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| Outline of Research at the Start |
The study will generate a mechanical microenvironment to direct iPSCs to generate embryo-like organoid called gastruloid without the use of exogenous chemical stimulation. The overall purpose to understand morphogenetic events taking place during tissue growth and elucidate neuromesodermal tissue specification.
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| Outline of Final Research Achievements |
This project introduces the application of a simple agarose-based cryogel that can trap iPSCs and confine them. Thus, compacted cells sense mechanical constraints and promote differentiation in a 3D growth phase without the use of specific morphogens. The aggregates showed features of embryonic development, which display Anterior/Posterior (A-P) axis development and the presence of three germ layers along the axial convergence. The detailed cell specification reveals the capacity to self-organize into a rudimentary neural fate along the A-P axis. Notably, the transition of core pluripotency protein Sox2+ cells to prime state pluripotency is marked by Otx2 which is in the state of the stable epiblast. Later, it contributes to promoting mutually exclusive patterns between Otx2 and T-Bra. Thus, these findings can provide new insight into iPScs/material interaction in promoting neuromesodermal fate in an embryonic context.
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| Academic Significance and Societal Importance of the Research Achievements |
The projects provide a simple approach that highlights cell/material interface platform. This platform can generate embryonic organoid derived from iPSCs. Further, useful to scale up to an organoid-on-chip model for drug testing to prevent fetal toxicity and miscarriage.
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