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Transcriptional Regulation of Cardiac Myocytes during Fetal to Neonatal Transition
Author(s) -
Addis Caroline Rebecca,
Lemley Aubrey L,
Jani Sarin,
Fresco Victor,
Argraves Scott,
Goodwin Richard
Publication year - 2006
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.20.4.a26
Subject(s) - wnt signaling pathway , biology , transcriptome , gene expression , microbiology and biotechnology , microrna , myocyte , microarray analysis techniques , heart development , cell cycle , transcriptional regulation , regulation of gene expression , cell growth , gene , cardiac myocyte , embryonic stem cell , signal transduction , genetics
Cardiac mass during fetal life increases primarily due to cardiac myocyte (CM) proliferation. Postnatally there is a hyperplastic to hypertrophic transition in which most CMs withdraw from the cell cycle. Here, we have investigated gene regulation that accompanies CM cell division withdrawal by performing a large‐scale study of transcriptional regulation of transitioning CMs in vivo. Using Affymetrix microarrays and validation with QRT‐PCR, some of the key regulators of this transition were elucidated. Immunohistochemistry validated the protein expression patterns of transcriptionally altered genes. RNA was isolated from embryonic day 15 rat ventricular CMs and compared to neonatal day 3 CM RNA to determine gene expression changes during this transition. Statistical analysis of this data compiled a list of 453 genes that had a fold change of two or higher. One gene found was IL‐6, part of a family of cytokines has been implicated in many inflammatory responses, but not in CM proliferation. One IL‐6 family member, cardiotrophin‐1, has been linked to the inflammatory response after MI. Components of the Jak‐STAT, Wnt, and TGF‐beta signaling pathways, were implicated in our screen. Other notable genes found in the analysis are Jumonji and Sprouty1, which are new to the field of heart development. Analysis of the transcriptomes of cycling and non‐cycling cardiac myocytes has enabled the delineation of regulatory pathways that control CM cell division and differentiation. These findings set the stage for detailed analysis of the pathways, possibly allowing for novel interventions that could enhance CM proliferation.