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Deciphering the Molecular Foundations and Functional Competence of Alternative Human Naïve Pluripotent Stem Cells

Objective

An important goal of stem cell therapy is to create “customized” cells that are genetically identical to the patient, which upon transplantation can restore damaged tissues. Such cells can be obtained by in vitro direct reprogramming of somatic cells into embryonic stem (ES)-like cells, termed induced pluripotent stem cells (iPSC). This approach also opens possibilities for modelling human diseases in vitro. However, major hurdles remain that restrain fulfilling conventional human iPSC/ESC potential, as they reside in an advanced primed pluripotent state. Such hurdles include limited differentiation capacity and functional variability. Further, in vitro iPSC based research platforms are simplistic and iPSC based “humanized” chimeric mouse models may be of great benefit.
The recent isolation of distinct and new “mouse-like” naive pluripotent states in humans that correspond to earlier embryonic developmental state(s), constitutes a paradigm shift and may alleviate limitations of conventional primed iPSCs/ESCs. Thus, our proposal aims at dissecting the human naïve pluripotent state(s) and to unveil pathways that facilitate their unique identity and flexible programming.
Specific goals: 1) Transcriptional and Epigenetic Design Principles of Human Naïve Pluripotency 2) Signalling Principles Governing Human Naïve Pluripotency Maintenance and Differentiation 3) Defining Functional Competence and Safety of Human Naïve Pluripotent Stem Cells in vitro 4) Novel human naïve iPSC based cross-species chimeric mice for studying human differentiation and disease modelling in vivo. These aims will be conducted by utilizing engineered human iPSC/ESC models, CRISPR/Cas9 genome-wide screening, advanced microscopy and ex-vivo whole embryo culture methods. Our goals will synergistically lead to the design of strategies that will accelerate the safe medical application of human naive pluripotent stem cells and their use in disease specific modelling and applied stem cell research.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-COG - Consolidator Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2016-COG

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Host institution

WEIZMANN INSTITUTE OF SCIENCE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 000 000,00
Address
HERZL STREET 234
7610001 Rehovot
Israel

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Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 000 000,00

Beneficiaries (1)

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