Transcriptional features of biological age maintained in human cultured cardiac interstitial cells.

Abstract

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.