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Signal to Regeneration

Project description

Potential cellular mechanisms of mammalian limb regeneration

Some animals, such as salamanders, starfish and crabs, can regenerate limbs. Humans, so far, cannot, but scientists believe they may have the genetic machinery to do so. The ERC-funded SigReg project aims to investigate the potential of mammalian regeneration. Its previous ground-breaking work in amphibian cells and tissues enabled characterisation of epithelial cells’ ‘regenerative signaling centres’ and showed that similar cells exist across species, including in mammals. SigReg intends to determine how signalling centres interact with surrounding cell populations, how environmental cues help these centres to form, and whether grafted signalling-centre cells can trigger regeneration after amputation. To do so, it will leverage mammalian stem cell protocols, skin cultures, and adult mouse amputation models.

Objective

"One of the enduring questions in biology is understanding why mammals, unlike amphibians, are unable to regenerate their limbs. Recently, our knowledge of this fascinating and clinically relevant topic has evolved from tissue-level observations in amphibians to comprehensive cellular characterizations. My research was among the first to uncover the cellular composition of regeneration using single-cell RNA sequencing (scRNA-Seq), revealing the critical mechanisms of regenerative epithelial signaling center cell types (Aztekin et al., 2019, 2021). Building on this, my lab has established the equivalence of these cell types across species, including mammals (Zhong et al., 2023). Concurrently, we have developed novel, simplified models to probe their properties in detail (Aztekin et al., 2021; Skoufa et al., 2024).

The overarching goal of ""Signal to Regeneration"" (SigReg) is to determine the potential of mammalian regeneration by dissecting the properties of regenerative signaling center cell types. For this, we will employ our mammalian stem cell protocols, skin cultures, and adult mouse amputation models in combination with imaging and sequencing. SigReg will elucidate: (1) how signaling centers quantitatively and dynamically interact with other populations, (2) which environmental factors shape the epigenetic landscape to form regenerative signaling centers in adult mouse skin, and (3) whether grafting signaling center cells can induce regeneration programs following mouse digit amputations.

SigReg will establish the quantitative features of signaling centers while demonstrating the critical role of environmental and biomechanical factors in shaping a regenerative histone landscape in adult mice. By applying insights from amphibian studies to mammals, our findings have the potential to pave the way for inducing mammalian digit regeneration, potentially revolutionizing our understanding of regeneration and fueling research and the broader field for decades to come."

Fields of science (EuroSciVoc)

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Keywords

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2025-STG

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Host institution

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
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.

€ 1 834 883,00
Address
HOFGARTENSTRASSE 8
80539 MUNCHEN
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Research Organisations
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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.

€ 1 834 883,00

Beneficiaries (1)

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