DFG Collaborative Research Centre 1444 - Directed Cellular Self‐Organisation to Advance Bone Regeneration 

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DFG Collaborative Research Centre 1444

This Collaborative Research Centre aims to unravel the basic mechanisms that differentiate between success and failure in regeneration of musculoskeletal tissue using bone healing as a role model.

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Subproject 2 - Principal Investgators

Prof. Dr. Hans-Dieter Volk

CRC 1444 Deputy Spokesperson & Ombudsperson, Subprojects 1 & 2 | RU Subproject 5

Impact of epigenetic regulation on T subsets involved in bone fracture healing

Polansky-Biskup and Volk are investigating which impact epigenetic regulation has on T subsets involved in bone fracture healing. The aim is to identify the critical epigenetic players ('epigenetic switch regions') driving the differentiation, migration and function of the harmful pro-inflammatory effector T cells (Teff) and the beneficial regulatory T cells (Treg) during successful or impaired bone regeneration. For this, Polansky-Biskup and Volk are generating detailed molecular signatures (epigenome, transcriptome, surface proteome, T cell receptor profile) of primary human Teff and Treg cells from ex vivo material from bone fracture patients. In addition, the impact of proliferation-induced senescence mechanisms imprinted in the epigenome is being analyzed in the relevant T cell subsets.  

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Most important results

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Single-cell multiomics profiling

Inflammatory Response | Force Transmission & Sensing

Single-cell multiomics profiling of T cell subsets, which negatively impact bone regeneration.

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DNA methylome

Inflammatory Response | Force Transmission & Sensing

Proliferation-induced cellular senescence in T cells is imprinted in the DNA methylome.

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Enhancer landscape

Inflammatory Response | Force Transmission & Sensing

The enhancer landscape predetermines the skeletal regeneration capacity of stromal cells.

Hochmann et al. Sci Transl Med. 2023 | In collaboration with P05 and P16

Team

Anamika Giri (Postdoc)

Computational analysis of single cell TEA (Transcriptome, Epitopes, Accessibility) sequencing data of T lymphocyte subsets

Frederik Hamm (Doctoral Researcher)

Epigenetically imprinted senescence in T lymphocytes

Iuliia Kotko (MD Candidate)

Deep cellular and molecular phenotyping of T lymphocytes

Stephan Schlickeiser (Senior Scientist)

Single-cell multiomics analysis of T lymphocyte subsets

Désirée Jacqueline Wendering (Postdoc)

Profiling of T lymphocyte subsets using various single-cell multiomics techniques

Publications

  • Hochmann, S.; Ou, K.; Poupardin, R.; Mittermeir, M.; Textor, M.; Ali, S.; Wolf, M.; Ellinghaus, A.; Jacobi, D.; Elmiger, J. A. J.; Donsante, S.; Riminucci, M.; Schafer, R.; Kornak, U.; Klein, O.; Schallmoser, K.; Schmidt-Bleek, K.; Duda, G. N.; Polansky, J. K.; Geissler, S.; Strunk, D.


    The enhancer landscape predetermines the skeletal regeneration capacity of stromal cells

    Sci Transl Med 2023; 15(688):eabm7477.

 

 

 

 

Founded by the DFG (Project Number: 427826188)
Funding Period 2021-2024