Return of the Tbx5; lineage-tracing reveals ventricular cardiomyocyte-like precursors in the injured adult mammalian heart

Article


Siatra, P., Vatsellas, G., Chatzianastasiou, A., Balafas, E., Manolakou, T., Papapetropoulos, A., Agapaki, A., Mouchtouri, A-T., Ruchaya, P. J., Korovesi, A. G., Mavroidis, M., Thanos, D., Beis, D. and Kokkinopoulos, I. 2023. Return of the Tbx5; lineage-tracing reveals ventricular cardiomyocyte-like precursors in the injured adult mammalian heart. NPJ Regenerative Medicine. 8 (Art. 13). https://doi.org/10.1038/s41536-023-00280-9
AuthorsSiatra, P., Vatsellas, G., Chatzianastasiou, A., Balafas, E., Manolakou, T., Papapetropoulos, A., Agapaki, A., Mouchtouri, A-T., Ruchaya, P. J., Korovesi, A. G., Mavroidis, M., Thanos, D., Beis, D. and Kokkinopoulos, I.
Abstract

The single curative measure for heart failure patients is a heart transplantation, which is limited due to a shortage of donors, the need for immunosuppression and economic costs. Therefore, there is an urgent unmet need for identifying cell populations capable of cardiac regeneration that we will be able to trace and monitor. Injury to the adult mammalian cardiac muscle, often leads to a heart attack through the irreversible loss of a large number of cardiomyocytes, due to an idle regenerative capability. Recent reports in zebrafish indicate that Tbx5a is a vital transcription factor for cardiomyocyte regeneration. Preclinical data underscore the cardioprotective role of Tbx5 upon heart failure. Data from our earlier murine developmental studies have identified a prominent unipotent Tbx5-expressing embryonic cardiac precursor cell population able to form cardiomyocytes, in vivo, in vitro and ex vivo. Using a developmental approach to an adult heart injury model and by employing a lineage-tracing mouse model as well as the use of single-cell RNA-seq technology, we identify a Tbx5-expressing ventricular cardiomyocyte-like precursor population, in the injured adult mammalian heart. The transcriptional profile of that precursor cell population is closer to that of neonatal than embryonic cardiomyocyte precursors. Tbx5, a cardinal cardiac development transcription factor, lies in the center of a ventricular adult precursor cell population, which seems to be affected by neurohormonal spatiotemporal cues. The identification of a Tbx5-specific cardiomyocyte precursor-like cell population, which is capable of dedifferentiating and potentially deploying a cardiomyocyte regenerative program, provides a clear target cell population for translationally-relevant heart interventional studies.

JournalNPJ Regenerative Medicine
Journal citation8 (Art. 13)
ISSN2057-3995
Year2023
PublisherNature Research
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Digital Object Identifier (DOI)https://doi.org/10.1038/s41536-023-00280-9
Web address (URL)https://www.nature.com/articles/s41536-023-00280-9
Publication dates
Online03 Mar 2023
Publication process dates
Accepted25 Jan 2023
Deposited12 Jun 2023
FunderHellenic Foundation for Research and Innovation (HFRI)
Copyright holder© 2023, The Authors
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