Ex vivo expansion of cells is necessary in regenerative medicine to generate large populations for therapeutic use. Adaptation to culture conditions prompt an increase in transcriptome diversity and decreased population heterogeneity in cKit+ cardiac interstitial cells (cCICs). The “transcriptional memory” influenced by cellular origin remained unexplored and is likely to differ between neonatal versus senescent input cells undergoing culture expansion. Transcriptional profiles derived from single cell RNASEQ platforms characterized human cCIC derived from neonatal and adult source tissue. Bioinformatic analysis revealed contrasting imprint of age influencing targets of 1) cell cycle, 2) senescence associated secretory phenotype (SASP), 3) RNA transport, and 4) ECM-receptor/fibrosis. A small subset of cCICs exist in a transcriptional continuum between “youthful” phenotype and the damaged microenvironment of LVAD tissue in which they were embedded. The connate transcriptional phenotypes offer fundamental biological insight and highlights cellular input as a consideration in culture expansion and adoptive transfer protocols.

细胞的离体扩增在再生医学中是必要的，以产生大量用于治疗用途的细胞群。适应培养条件促进转录组多样性的增加和 cKit+ 心脏间质细胞 (cCIC) 的群体异质性降低。受细胞起源影响的“转录记忆”仍未被探索，并且可能在新生输入细胞与经历培养扩增的衰老输入细胞之间存在差异。源自单细胞 RNASEQ 平台的转录谱表征了源自新生儿和成人来源组织的人类 cCIC。生物信息学分析揭示了年龄影响目标的对比印记：1) 细胞周期、2) 衰老相关分泌表型 (SASP)、3) RNA 转运和 4) ECM 受体/纤维化。一小部分 cCIC 存在于“年轻”表型和它们所嵌入的 LVAD 组织受损微环境之间的转录连续体中。先天转录表型提供了基本的生物学洞察力，并突出了细胞输入作为培养扩展和过继转移协议的考虑因素。