Normal adult liver is uniquely capable of renewal
and repair after injury. Whether this response
represents simple hyperplasia of various liver elements
or requires recapitulation of the genetic program of
the developing liver is not known. To study these possibilities,
we examined transcriptional programs of
adult liver after partial hepatectomy and contrasted
these with developing embryonic liver. Principal component
analysis demonstrated that the time series of
gene expression during liver regeneration does not segregate
according to developmental transcription patterns.
Gene ontology analysis revealed that liver restoration
after hepatectomy and liver development differ
dramatically with regard to transcription factors
and chromatin structure modification. In contrast, the
tissues are similar with regard to proliferationassociated
genes. Consistent with these findings, realtime
polymerase chain reaction showed transcription
factors known to be important in liver development
are not induced during liver regeneration. These three
lines of evidence suggest that at a transcriptional level,
restoration of liver mass after injury is best described
as hepatocyte hyperplasia and not true regeneration.
We speculate this novel pattern of gene expression may
underlie the unique capacity of the liver to repair itself
after injury.
Keywords: time course
Overall design: In order to elucidate the molecular similarities between regenerating and developing liver, we performed high-density microarray analysis using Affymetrix MG 430 2.0 chips for targets at 0, 1, 2, 6, 12, 18, 24, 30, 48, and 72 hours after partial hepatectomy and at 10.5, 11.5, 12.5, 13.5, 14.5, and 16.5 days post conception (dpc).
Each experimental time point is represented by two separate samples, each consisting of at least 3 pooled tissues from different animals. For example, 6 hepatectomies were performed for the 1 hour post-hepatectomy time point. Time 0 is used as control.
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