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Tytuł:
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Transcriptional features of biological age maintained in human cultured cardiac interstitial cells.
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Autorzy:
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Echeagaray O; San Diego Heart Research Institute and Integrated Regenerative Research Institute, San Diego State University, San Diego, CA 92182-4650, USA.
Kim T; San Diego Heart Research Institute and Integrated Regenerative Research Institute, San Diego State University, San Diego, CA 92182-4650, USA.
Casillas A; San Diego Heart Research Institute and Integrated Regenerative Research Institute, San Diego State University, San Diego, CA 92182-4650, USA.
Monsanto M; San Diego Heart Research Institute and Integrated Regenerative Research Institute, San Diego State University, San Diego, CA 92182-4650, USA.
Sussman M; San Diego Heart Research Institute and Integrated Regenerative Research Institute, San Diego State University, San Diego, CA 92182-4650, USA. Electronic address: .
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Źródło:
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Genomics [Genomics] 2021 Nov; Vol. 113 (6), pp. 3705-3717. Date of Electronic Publication: 2021 Sep 09.
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Typ publikacji:
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Journal Article; Research Support, N.I.H., Extramural
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Język:
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English
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Imprint Name(s):
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Original Publication: San Diego : Academic Press, [c1987-
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MeSH Terms:
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Cellular Senescence*/genetics
Transcriptome*
Cells, Cultured ; Computational Biology ; Humans ; Phenotype
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Grant Information:
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R01 HL135661 United States HL NHLBI NIH HHS; R01 HL067245 United States HL NHLBI NIH HHS; R01 HL105759 United States HL NHLBI NIH HHS
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Contributed Indexing:
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Keywords: Biological age; Culture adaptation; In vitro expansion; Senescence; Single cell RNASEQ; Transcriptional memory
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Entry Date(s):
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Date Created: 20210912 Date Completed: 20220331 Latest Revision: 20220401
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Update Code:
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20240105
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DOI:
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10.1016/j.ygeno.2021.09.004
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PMID:
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34509618
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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.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
