Construction of bioinformatic infrastructure for transcriptomic analysis to improve induced pluripotent stem cell systems

Objective:

The project aims to use computational methods to enhance the maturation of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) for clinical applications. By identifying the critical differences between immature iPSC-CMs and mature adult cardiomyocytes (CMs), the project seeks to develop bioinformatic solutions that will facilitate the maturation of iPSC-CMs, thereby improving their potential for therapeutic use in patients who have suffered myocardial infarction.

Methods:

The project will employ state-of-the-art single-cell sequencing technology to analyze and compare gene expression profiles of iPSC-CMs and adult CMs. This includes identifying key transcriptional regulators and metabolites responsible for the maturation process, and optimizing oxygen tension conditions for iPSC-CM maturation. Bioinformatic tools and computational pipelines will be developed and used to interpret the single-cell sequencing data, leading to the creation of generic pipelines for broader application in stem cell research.

Single Cell

Expected outcomes:

  • Identification of critical transcriptional regulators and metabolites that enhance iPSC-CM maturation.
  • Development of bioinformatic pipelines that can be marketed as services for single-cell sequencing analysis.
  • Improved protocols for iPSC differentiation that can be applied to various cell types, advancing stem cell research and potential clinical therapies.

Significance:

This project holds significant potential for advancing regenerative medicine by addressing the current limitations in iPSC-CM maturation. Successful outcomes could lead to more effective therapies for heart attack patients, reducing mortality and improving quality of life.

Keywords: bioinformatics, single cell RNA sequencing, iPSC-CMs, cardiomyocytes, stem cell maturation, regenerative medicine, myocardial infarction

PhD candidate Frederik A. Bjerre

In collaboration with Prof. Ditte C. Andersen at University of Southern Denmark.

Financed by Innovation Fund Denmark.