Multicellular Human Cardiac Organoids Transcriptomically Model Distinct Tissue-Level Features of Adult Myocardium.
Multicellular Human Cardiac Organoids Transcriptomically Model Distinct Tissue-Level Features of Adult Myocardium.
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DOI：
10.3390/ijms22168482
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发表时间：
2021-08-06
影响因子：
5.6
通讯作者：
Mei Y
中科院分区：
文献类型：
--
作者：
Kerr CM;Richards D;Menick DR;Deleon-Pennell KY;Mei Y
人诱导多能干细胞衍生的心肌细胞（hiPSC-CM）已被广泛用于疾病建模和药物心脏毒性筛选。为此，我们最近开发了人类心脏类器官（hCO）用于模拟人类心肌。在这里，我们对各种体外hiPSC-CM平台（2D iPSC-CM、3D iPSC-CM和hCO）进行转录组学分析，以推断这些体外模型的优势和局限性。我们进一步比较了iPSC-CM模型与人心肌样品。我们的数据显示，3D hiPSC-CM和hCO的3D体外环境刺激与组织形成相关的基因的表达。与仅hiPSC-CM的模型相比，hCO表现出多种生理学相关的细胞功能。在hCO中包括其他心脏细胞类型导致与成人心肌更多的转录组相似性。hCO缺乏成熟的心肌细胞和免疫细胞，这限制了人类成年心肌的完全复制。总之，3D hCO在转录组学上与心肌相似，工程化3D心脏模型的未来发展将受益于多样化的细胞群，特别是免疫细胞。
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been widely used for disease modeling and drug cardiotoxicity screening. To this end, we recently developed human cardiac organoids (hCOs) for modeling human myocardium. Here, we perform a transcriptomic analysis of various in vitro hiPSC-CM platforms (2D iPSC-CM, 3D iPSC-CM and hCOs) to deduce the strengths and limitations of these in vitro models. We further compared iPSC-CM models to human myocardium samples. Our data show that the 3D in vitro environment of 3D hiPSC-CMs and hCOs stimulates the expression of genes associated with tissue formation. The hCOs demonstrated diverse physiologically relevant cellular functions compared to the hiPSC-CM only models. Including other cardiac cell types within hCOs led to more transcriptomic similarities to adult myocardium. hCOs lack matured cardiomyocytes and immune cells, which limits a complete replication of human adult myocardium. In conclusion, 3D hCOs are transcriptomically similar to myocardium, and future developments of engineered 3D cardiac models would benefit from diversifying cell populations, especially immune cells.