# Critical Role of TBX20 in Cardiomyocyte Maturation during Direct Cardiac Reprogramming

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2022 · $371,250

## Abstract

SUMMARY
Direct cardiac reprogramming to generated induced cardiomyocytes (iCMs) from fibroblasts has emerged as a
promising therapeutic strategy for the treatment of heart failure, which is still the leading cause of mortality and
morbidity in the developed country. While much is known regarding iCMs generated from mouse cells, the
adaptation of direct cardiac reprogramming to human cells is hurdled with low efficiency and poor quality
because of intrinsic differences between species. We recently reported the single cell transcriptomic analysis
during human cardiac reprogramming and discovered that the insufficient generation of iCMs is associated
with underdeveloped gene programs, such as ion channel and cell junction, suggesting that additional
reprogramming factors regulating function of cardiomyocytes might be required. In this research program, we
hypothesis that a novel reprogramming factor TBX20 plays an essential role to generate cardiomyocyte identity
by establishing gene programs associated with cardiomyocyte function. In support of our hypothesis, our
preliminary data have shown that TBX20 is largely under-expressed in human iCMs. While forced expression
of TBX20 significantly enhanced reprogramming efficiency accompanied with activation of gene programs
associated with cardiomyocyte function. To test the hypothesis, we propose to 1) further determine the impact
of TBX20 on direct human cardiac reprogramming and 2) determine how TBX20 functions as an essential
reprogramming factor during this process. The main objective of this proposal is to identify the critical role of
TBX20 on regeneration of cardiomyocytes during direct cardiac reprogramming. The completion of this
proposal will not only provide mechanistic insight into how cardiomyocyte identity can be regenerated by direct
cardiac reprogramming but also enable us to generate functional-reliable cardiomyocytes directly from human
non-myocytes for potential heart repair.

## Key facts

- **NIH application ID:** 10455734
- **Project number:** 5R01HL153220-03
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Yang Zhou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $371,250
- **Award type:** 5
- **Project period:** 2020-08-25 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455734

## Citation

> US National Institutes of Health, RePORTER application 10455734, Critical Role of TBX20 in Cardiomyocyte Maturation during Direct Cardiac Reprogramming (5R01HL153220-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10455734. Licensed CC0.

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