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High‐Resolution Chronology of Murine Biological Responses to 70% Partial Hepatectomy
Author(s) -
Barnhart Benjamin Karl,
Hengstler Jan G,
Hoek Jan B,
Vadigepalli Rajanikanth
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.496.44
Subject(s) - biology , liver regeneration , transcriptome , population , computational biology , microbiology and biotechnology , regeneration (biology) , gene expression , gene , genetics , medicine , environmental health
The regenerating liver orchestrates an organ‐wide reprogramming of transcription. This results in a precise recovery of liver mass by regulating not only cell cycle progression, but a diverse set of cell functions, metabolic, catabolic, immune, and lysosomal. Here, we attempt to create an organ‐scale, high‐resolution chronology of major biological processes affected by liver regeneration after 70% partial hepatectomy (PHx), with attention given to cell‐type population dynamics. A 70% PHx was performed on C57BL/6 mice and total RNA was isolated from liver tissue at 8 time points spanning 1 hour to 1 week post‐operation. A microarray (GeneChip™ Mouse Genome 430 2.0, Applied Biosystems) was used to quantify transcripts from the whole genome. Differential expression was calculated at each time point, and visualized using a novel pattern‐based approach developed by our lab. Sub‐clusters determined by patterns of expression were evaluated using the Database for Annotation, Visualization and Integrated Discovery (DAVID) bioinformatics resource (6.8), with specific focus on the biological process information from the Gene Ontology Consortium. Highly enriched annotations for specific processes were used as the basis for process entries on the biological timeline. Cell‐specific markers were identified among the differentially expressed genes to show the dynamics of macrophage and hepatic stellate cell activation. While pro‐inflammatory macrophage activity coincides with HSC activation, pro‐restorative macrophages activity grows slowly during recovery. Taken together, this detailed chronology of biological processes reveals the coordination of responses after partial hepatectomy, specifically the timing and coordination of non‐parenchymal cell activity. This information is critical for understanding how global transcriptional changes can regenerate and regulate liver mass, as well as for designing computational simulations at the molecular, cellular and organ‐level scales. Support or Funding Information Research was supported by NIH grant: 5U01EB023224‐02 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .