Gene expression in the human mammary epithelium during lactation: the milk fat globule transcriptome

Patricia D. Maningat, Partha Sen, Monique Rijnkels, Agneta L. Sunehag, Darryl L. Hadsell, Molly Bray, Morey W. Haymond

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

Maningat PD, Sen P, Rijnkels M, Sunehag AL, Hadsell DL, Bray M, Haymond MW. Gene expression in the human mammary epithelium during lactation: the milk fat globule transcriptome. Physiol Genomics 37: 12-22, 2009. First published November 18, 2008; doi:10.1152/physiolgenomics.90341.2008.-The molecular physiology underlying human milk production is largely unknown because of limitations in obtaining tissue samples. Determining gene expression in normal lactating women would be a potential step toward understanding why some women struggle with or fail at breastfeeding their infants. Recently, we demonstrated the utility of RNA obtained from breast milk fat globule (MFG) to detect mammary epithelial cell (MEC)-specific gene expression. We used MFG RNA to determine the gene expression profile of human MEC during lactation. Microarray studies were performed using Human Ref-8 BeadChip arrays (Illumina). MFG RNA was collected every3hfor 24 h from five healthy, exclusively breastfeeding women. We determined that 14,070 transcripts were expressed and represented the MFG transcriptome. According to GeneSpring GX 9, 156 ontology terms were enriched (corrected P < 0.05), which include cellular (n = 3,379 genes) and metabolic (n = 2,656) processes as the most significantly enriched biological process terms. The top networks and pathways were associated primarily with cellular activities most likely involved with milk synthesis. Multiple sampling over 24 h enabled us to demonstrate core circadian clock gene expression and the periodicity of 1,029 genes (7%) enriched for molecular functions involved in cell development, growth, proliferation, and cell morphology. In addition, we found that the MFG transcriptome was comparable to the metabolic gene expression profile described for the lactating mouse mammary gland. This paper is the first to describe the MFG transcrip- tome in sequential human samples over a 24 h period, providing valuable insights into gene expression in the human MEC.

Original languageEnglish (US)
Pages (from-to)12-22
Number of pages11
JournalPhysiological genomics
Volume37
Issue number1
DOIs
StatePublished - Mar 2009

Keywords

  • Breastfeeding
  • Circadian clock genes
  • Microarray

ASJC Scopus subject areas

  • Physiology
  • Genetics

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