Laboratory of Vascular Biology and Regenerative Medicine Centro Cardiologico Monzino IRCCS, Milano, 20138 Italy.
Del E. Webb Center for Neuroscience, Aging & Stem Cell Research, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, California 92037, USA.
Front Biosci (Landmark Ed). 2016 Jan 1;21(4):719-43. doi: 10.2741/4417.
Prior studies have demonstrated that founder cell type could influence induced pluripotent stem cells (iPSCs) molecular and developmental properties at early passages after establishing their pluripotent state. Herein, we evaluated the persistence of a functional memory related to the tissue of origin in iPSCs from syngeneic cardiac (CStC) vs skin stromal cells (SStCs). We found that, at passages greater than 15, iPSCs from cardiac stromal cells (C-iPSCs) produced a higher number of beating embryoid bodies than iPSCs from skin stromal cells (S-iPSCs). Flow cytometry analysis revealed that dissected beating areas from C-iPSCs exhibited more Troponin-T positive cells compared to S-iPSCs. Beating areas derived from C-iPSCs displayed higher expression of cardiac markers, more hyperpolarized diastolic potentials, larger action potential amplitude and higher contractility than beaters from skin. Also, different microRNA subsets were differentially modulated in CStCs vs SStCs during the reprogramming process, potentially accounting for the higher cardiogenic potentials of C-iPSCs vs S-iPSCs. Therefore, the present work supports the existence of a founder organ memory in iPSCs obtained from the stromal component of the origin tissue.
先前的研究表明，在建立多能状态后的早期传代中，起始细胞类型可能会影响诱导多能干细胞（iPSCs）的分子和发育特性。在此，我们评估了源自同种异体心脏（CStC）与皮肤基质细胞（SStCs）的 iPSCs 中与组织起源相关的功能记忆的持久性。我们发现，在传代超过 15 代后，源自心脏基质细胞（C-iPSCs）的 iPSCs 比源自皮肤基质细胞（S-iPSCs）的 iPSCs 产生更多的搏动类胚体。流式细胞术分析显示，与 S-iPSCs 相比，从 C-iPSCs 分离的搏动区域具有更多的肌钙蛋白-T 阳性细胞。源自 C-iPSCs 的搏动区域表现出比源自皮肤的搏动区域更高的心脏标志物表达水平、更超极化的舒张电位、更大的动作电位幅度和更高的收缩性。此外，在重编程过程中，CStCs 与 SStCs 之间的不同 microRNA 亚群存在差异调节，这可能解释了 C-iPSCs 比 S-iPSCs 具有更高的心脏生成潜能。因此，本工作支持源自起始组织基质成分的 iPSCs 中存在起始器官记忆的存在。
