library_construction_protocol: For RNA-seq, RNA from iPSCs, SMC-meso (Day 8) and CM-meso (Day 5) cells were extracted using Trizol reagents (300 μL per well of 6-well plate) according to manufacturer's protocol .For ChIP-seq, cells (Wildtype and MYOCD-mEGFP knock-in hiPSCs) were crosslinked with 4% PFA in PBS for 15 minutes and quenched with 0.125 M glycine for 10 minutes at room temperature. For mesodermal CMs, we use hiPSCs at cardiac lineage differentiation Day 5. For mesodermal SMCs, we use hiPSCs at smooth muscle lineage differentiation Day 8. Crosslinked samples were then washed with cold PBS. Samples were collected by a brief spin and treated with 10 mM Tris-HCl (pH 8.0), 10mM NaCl and 0.2% NP-40 for 30 minutes to collect nuclei. After nuclear extraction, chromatin was sheared on a Bioruptor Pico (Diagenode) for 16 cycles (30 sec on/ 30 sec off for each cycle) at 4°C in sonication buffer (0.1% SDS, 1% Triton X-100, 10 mM Tris-HCl, 1 mM EDTA, 0.1% sodium deoxycholate, 0.25% sarkosyl, 1 mM DTT, 1x cOmplete Protease Inhibitor Cocktail (Sigma, 11836170001) and 200 μM PMSF, pH 8.0). After sonication, 1% of the sonicated chromatin from each sample was taken out as 'Input' samples. Take 20 μL of sonicated sample from each group for electrophoresis on the 1% agarose gel for sonication efficiency and quality control. The remaining sonicated chromatin was evenly split for MYOCD-GFP or H3k27ac ChIP. NaCl was then added to a final concentration of 300 mM for histone ChIP and 150 mM for MYOCD-GFP ChIP. 1 μg/mL H3k27ac antibody (Diagenode, C15410196) or 10 μg/mL GFP antibody (Thermo Fisher Scientific, A-11122) was added to each sample and incubated at 4°C overnight with gentle rotation. The next day, 30 μL/mL of pre-washed Dynabeads Protein G (Invitrogen, 10004D) was added to each sample for a two-hour incubation. After that, the beads were washed twice with 1 mL RIPA 0 buffer (0.1% SDS, 1% Triton X-100, 10 mM Tris-HCl, 1 mM EDTA, 0.1% sodium deoxycholate, pH 8.0), twice with 1 mL RIPA 0.3 buffer (0.1% SDS, 1% Triton X-100, 10 mM Tris-HCl, 1 mM EDTA, 0.1% sodium deoxycholate, 300 mM NaCl, pH 8.0), twice with 1 mL LiCl wash buffer (250 mM LiCl, 0.5% IGEPAL CA-630, 0.5% sodium deoxycholate, 1 mM EDTA, 10 mM Tris-HCl, pH 8.0), and finally twice with 1 mL TE buffer (10 mM Tris-HCl, 1 mM EDTA, pH 8.0). For each ChIP sample or input sample, 100 μL of SDS elution buffer (1% SDS, 10 mM EDTA, 50 mM Tris-HCl, pH 8.0) was added and incubation was done at 65°C overnight on a ThermoMixer (Eppendorf) at 1,000 RPM. The next day, supernatant was collected and further treated with 0.5 μg RNaseA (Sigma, 11119915001) for 30 minutes at 37°C, followed by 20 μg Proteinase K (NEB, P8107S) treatment at 37°C for 2 hours. DNA was recovered using MinElute PCR Purification Kit (QIAGEN, 28004) according to manufacturer's protocol. For RNA-seq, stranded mRNA-Seq libraries were generated using KAPA mRNA HyperPrep Kit (Roche, KK8581) following manufacturer's protocol. Sequencing was performed on an Illumina Nextseq 500 system for 1x75bp single-end sequencing. For ChIP-seq, libraries were prepared using the NEBNext Ultra II DNA Library Preparation Kit complemented with NEBNext Multiplex Oligos for Illumina from NEB (NEB, E6177S). 10 ng of DNA was used as starting material for Input samples and 1 ng for IP samples. Libraries were amplified using 12 cycles for Input samples and 15 cycles for IP samples on the thermocycler. Post amplification libraries were size selected at 250-450 bp in length using SPRISelect beads from Beckman Coulter. Libraries were validated using the Agilent D1000 ScreenTape.