Pharmacology and Toxicology > Research

Regenerative Pharmacology

Principal Investigator. Dr. med. et rer. nat. habil. Olaf Bergmann

About us

The loss of cardiomyocytes as a result of heart disease and injury is a major cause of morbidity and mortality. We have shown, using retrospective 14C birth dating¹, that cardiomyocyte renewal in humans continues at a low level throughout life^2,3. This finding has opened up the possibility of increasing cardiomyocyte renewal in heart disease by elucidating the underlying cellular and molecular mechanisms of cardiomyocyte proliferation. Our group focuses on understanding human cardiomyocyte renewal and loss during biological aging and disease using stem cell-derived cardiomyocytes and the development of complex cell-based models. We aim to investigate the impact of cell type composition, cell-cell interaction, cell cycle dynamics, and maturation of cardiomyocytes on heart regeneration. Our group uses customized cell cycle indicators to dissect the transcriptional patterns required to regulate cell division and use compound libraries to identify pro-proliferative small molecules^4,5. The overall goal is to identify fundamental mechanisms of regeneration that can be translated to improve the function of the diseased human heart.

References

1. Heinke, P., Rost, F., Rode, J., Trus, P., Simonova, I., Lázár, E., Feddema, J., Welsch, T., Alkass, K., Salehpour, M., et al. (2022). Diploid hepatocytes drive physiological liver renewal in adult humans. Cell Systems. 10.1016/j.cels.2022.05.001.

2. Bergmann, O., Bhardwaj, R.D., Bernard, S., Zdunek, S., Barnabe-Heider, F., Walsh, S., Zupicich, J., Alkass, K., Buchholz, B.A., Druid, H., et al. (2009). Evidence for Cardiomyocyte Renewal in Humans. Science 324, 98–102.

3. Bergmann, O., Zdunek, S., Felker, A., Salehpour, M., Alkass, K., Bernard, S., Sjostrom, S.L., Szewczykowska, M., Jackowska, T., Remedios, C.D., et al. (2015). Dynamics of Cell Generation and Turnover in the Human Heart. Cell, 1566–1575.

4. Baniol, M., Murganti, F., Smialowska, A., Panula, J., Lázár, E., Brockman, V., Giatrellis, S., Derks, W., and Bergmann, O. (2021). Identification and characterization of distinct cell cycle stages in cardiomyocytes using the FUCCI transgenic system. Exp. Cell Res., 112880.

5. Murganti, F., Derks, W., Baniol, M., Simonova, I., Trus, P., Neumann, K., Khattak, S., Guan, K., and Bergmann, O. (2022). FUCCI-Based Live Imaging Platform Reveals Cell Cycle Dynamics and Identifies Pro-proliferative Compounds in Human iPSC-Derived Cardiomyocytes. Frontiers in Cardiovascular Medicine 9. 10.3389/fcvm.2022.840147.

6. Derks, W., and Bergmann, O. (2020). Polyploidy in Cardiomyocytes: Roadblock to Heart Regeneration? Circ. Res. 126, 552–565.

Mitotic activity in neonatal cardiomyocytes. Staining with phospho-histone H3 identifies mitotic activity in non-cardiomyocytes (white) and in one cardiomyocyte (white/green). Nuclei are stained in blue. Image: Wouter Derks

Isolated mono and multinucleated cardiomyocytes. Many cardiomyocytes have multiple nuclei, which is very uncommon for somatic cells. Multinucleation is suggested to be a block cell division6. We have visualized the striated pattern of sarcomeres (red) and gap junctions (yellow). Nuclei are stained in blue. Image: Wouter Derks

Research Group Leader Regenerative PharmacologyDr. med. et rer. nat. habil. Olaf Bergmann

contact information

telephone: +49 551 3913247
e-mail address: olaf.bergmann(at)med.uni-goettingen.de
location: 4.E1. 328

ORCID: 0000-0003-1065-4107
CV

Selected Publications

Lundquist A, Lázár E, Han NS, Emanuelsson EB, Reitzner SM, Chapman MA, Shirokova V, Alkass K, Druid H, Petri S, Sundberg CJ, Bergmann O. FiNuTyper: design and validation of an automated deep learning-based platform for simultaneous fiber and nucleus type analysis in human skeletal muscle. Acta Physiol (Oxf). 2023 Apr 25:e13982. doi: 10.1111/apha.13982. PMID: 37097015.
Heinke P, Rost F, Rode J, Trus P, Simonova I, Lázár E, Feddema J, Welsch T, Alkass K, Salehpour M, Zimmermann A, Seehofer D, Possnert G, Damm G, Druid H, Brusch L, Bergmann O. Diploid hepatocytes drive physiological liver renewal in adult humans. Cell Syst. 2022 Jun 15;13(6):499-507.e12. doi: 10.1016/j.cels.2022.05.001. Epub 2022 May 31.
Murganti F, Derks W, Baniol M, Simonova I, Trus P, Neumann K, Khattak S, Guan K, Bergmann O. FUCCI-Based Live Imaging Platform Reveals Cell Cycle Dynamics and Identifies Pro-proliferative Compounds in Human iPSC-Derived Cardiomyocytes. Front Cardiovasc Med. 2022 Apr 25;9:840147. doi: 10.3389/fcvm.2022.840147.
Alkass K, Panula J, Westman M, Wu TD, Guerquin-Kern JL, Bergmann O. No Evidence for Cardiomyocyte Number Expansion in Preadolescent Mice. Cell. 2015 Nov 5;163(4):1026-36.
Bergmann, O. *§, S. Zdunek§, A. Felker, M. Salehpour, K. Alkass, S. Bernard, S. L. Sjostrom, M. Szewczykowska, T. Jackowska, C. G. Dos Remedios, T. Malm, M. Andrä, R. Jashari, J. R. Nyengaard, G. Possnert, S. Jovinge, H. Druid and J. Frisén. Dynamics of cell generation and turnover in the human heart. Cell. 2015 Jun 18;161(7):1566-75.