Macrophage Precursor Cells from the Left Atrial Appendage of the Adult Heart Spontaneously Reprogram into a C-kit+/CD45- Stem Cell-Like Phenotype [RNA-Seq]

The developmental origin of the c-kit expressing progenitor cell pool in the adult heart has remained elusive. Recently, it has been discovered that the injured heart is enriched with c-kit+ cells, which also express the hematopoietic marker CD45. In this study, we characterize the phenotype and transcriptome of the c-kit+/CD45+ cell population, originating from the left atrial appendage. These cells are defined as cardiac macrophage progenitors. We also demonstrate that the c-kit+/CD45+ progenitor cell population activates heart development, neural crest and pluripotency associated pathways in vitro, in conjunction with CD45 down-regulation, and acquire a c-kit+/lin- phenotype. This spontaneous reprogramming progresses further to a highly proliferative, partially myogenic phenotype. Our data suggests that c-kit+/lin- cells and cardiac macrophages have a common lineage origin possibly resolving some current conundrums in the field of cardiac regeneration. Two different stem cell types were grown by altering the tissue digestion protocol, from which one type was spontaneously transdifferentiating to other cell types. To investigate their transcriptional profiles we prepared RNA from two cell sorted replicates per cell type (A, B, C1, C2, C3).成年心脏中表达c-kit的祖细胞池的发育起源长期以来始终不明。近期研究发现，受损心脏中富集有同时表达造血标志物CD45的c-kit阳性细胞。本研究对源自左心耳的c-kit+/CD45+细胞群的表型与转录组进行了系统表征，该类细胞被定义为心脏巨噬细胞祖细胞。研究同时证实，在体外环境中，该c-kit+/CD45+祖细胞群可在CD45表达下调的同时，激活心脏发育、神经嵴及多能性相关通路，并获得c-kit+/lin-表型。这种自发重编程过程可进一步进展为高增殖性、部分肌源性的表型。本研究数据表明，c-kit+/lin-细胞与心脏巨噬细胞拥有共同的谱系起源，这或可解决心脏再生领域目前存在的若干学术难题。研究人员通过调整组织消化方案，成功培养出两种不同的干细胞类型，其中一类可自发向其他细胞类型转分化。为探究二者的转录谱特征，研究人员针对每种细胞类型（A、B、C1、C2、C3）分别制备了两份经细胞分选的RNA重复样本。