Cell barcoding reveals lineage-dependent outcomes in hiPSC cardiac differentiation
Sogu Sohn1, Daylin Morgan1, Cody Callahan1
1Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712-0238, United States.
Stem Cells (Dayton, Ohio)
|April 9, 2026
Summary
Tracking human induced pluripotent stem cell (hiPSC) clonal heterogeneity improves cardiac differentiation. Specific hiPSC lineages show distinct differentiation fates, impacting outcomes for cardiovascular disease treatments.
Area of Science:
- Stem Cell Biology
- Cardiovascular Research
- Developmental Biology
Background:
- Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) show promise for cardiovascular disease treatment.
- Clinical translation is hindered by heterogeneous differentiation outcomes due to complex molecular interactions.
- Current methods lack adequate control over these interactions, leading to variable results.
Purpose of the Study:
- To investigate the role of clonal lineage-dependent responses (fate priming) in hiPSC cardiac differentiation.
- To determine if controlling hiPSC clonal heterogeneity can improve differentiation outcomes.
- To address the overlooked variable of hiPSC clonal heterogeneity in cardiac differentiation protocols.
Main Methods:
- Utilized the ClonMapper cell barcoding platform to label, track, and isolate distinct hiPSC lineages from a single cell line.
- Compared cardiac differentiation outcomes between isolated single-clone hiPSC populations and heterogeneous multi-clone hiPSC populations.
- Analyzed lineage-specific differentiation preferences towards cardiomyocytes (CMs) or non-cardiomyocytes.
Main Results:
- Demonstrated that specific hiPSC lineages exhibit preferential differentiation into hiPSC-CMs or non-CMs, indicating fate priming.
- Observed significant differences in cardiac differentiation outcomes between single-clone populations exhibiting fate priming and heterogeneous populations.
- Confirmed that hiPSC lineage identity influences the efficiency and outcome of cardiac differentiation.
Conclusions:
- hiPSC clonal heterogeneity is a critical factor influencing cardiac differentiation efficiency and outcome.
- Targeting and controlling hiPSC lineage identity can potentially optimize hiPSC-CM production for therapeutic applications.
- Understanding and leveraging fate priming in hiPSC cardiac differentiation is essential for advancing cardiovascular regenerative medicine.
