Renjun Zhu

1 Introduction Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide [1], of which 20% has metastasised at presentation [2]. Although synthetic treatments have demonstrated substantially increased cancer survival during the past 40 years, the 5-year survival rate of CRC only increased from 51% to 65% [3]. The status of 5-fluorouracil (5-Fu) as a significant treatment for CRC is unshakable in neoadjuvant, adjuvant, or palliative therapies [4].

TF enrichment analysis (Figures 1K, 4D, 4F, 5G) was done using WebGestalt 2019, performing over-representation using the “transcription factor target” database. We started by selecting all TFs with FDR < 0.05. This generally produced a list with significant redundancy; we used different approaches to handle the redundancy depending on the situation. In Figure 1K, we first took all TFs identified as enriched for each cluster (or group of clusters, in the case of LA1 + LA2).

Highlights • Decellularized myocardial slices were repopulated with hiPSC-CMs to make EHS • EHS exhibited coordinated contractions and anisotropic electrical conduction • EHS were cultured and retained electrical and contractile function for >200 days • EHS had different sensitivities to ion channel drugs than cell monolayers Summary Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for cardiac studies, but their structural and functional immaturity...