Details

Autor(en) / Beteiligte

• Churko, Jared M
• Garg, Priyanka
• Treutlein, Barbara
• Venkatasubramanian, Meenakshi
• Wu, Haodi
• Lee, Jaecheol
• Wessells, Quinton N
• Chen, Shih-Yu
• Chen, Wen-Yi
• Chetal, Kashish
• Mantalas, Gary
• Neff, Norma
• Jabart, Eric
• Sharma, Arun
• Nolan, Garry P
• Salomonis, Nathan
• Wu, Joseph C

Titel

Defining human cardiac transcription factor hierarchies using integrated single-cell heterogeneity analysis

Ist Teil von

• Nature communications, 2018-11, Vol.9 (1), p.4906-14, Article 4906

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have become a powerful tool for human disease modeling and therapeutic testing. However, their use remains limited by their immaturity and heterogeneity. To characterize the source of this heterogeneity, we applied complementary single-cell RNA-seq and bulk RNA-seq technologies over time during hiPSC cardiac differentiation and in the adult heart. Using integrated transcriptomic and splicing analysis, more than half a dozen distinct single-cell populations were observed, several of which were coincident at a single time-point, day 30 of differentiation. To dissect the role of distinct cardiac transcriptional regulators associated with each cell population, we systematically tested the effect of a gain or loss of three transcription factors (NR2F2, TBX5, and HEY2), using CRISPR genome editing and ChIP-seq, in conjunction with patch clamp, calcium imaging, and CyTOF analysis. These targets, data, and integrative genomics analysis methods provide a powerful platform for understanding in vitro cellular heterogeneity.