Investigating the effect of positional variation on mid-lactation mammary gland transcriptomics in mice fed either a low-fat or high-fat diet

PLoS One. 2021 Aug 26;16(8):e0255770. doi: 10.1371/journal.pone.0255770. eCollection 2021.

Abstract

Little attention has been given to the effect of positional variation of gene expression in the mammary gland. However, more research is shedding light regarding the physiological differences that mammary gland location can have on the murine mammary gland. Here we examined the differentially expressed genes between mammary gland positions under either a low-fat diet (LFD) or a high-fat diet (HFD) in the mid-lactation mammary gland (lactation day 11; L11). Three-week old WT C57BL/6 mice were randomly assigned to either a low-fat diet (LFD) or high fat diet (HFD) (n = 3/group) and either the right thoracic mammary gland (TMG) or inguinal mammary gland (IMG) was collected from each dam for a total of 12 unique glands. Within each diet, differentially expressed genes (DEGs) were first filtered by adjusted p-value (cutoff ≤ 0.05) and fold-change (FC, cutoff ≥2). Genes were further filtered by mean normalized read count with a cutoff≥10. We observed that mammary gland position had a significant impact on mammary gland gene expression with either LFD or HFD diet, with 1264 DEGs in LFD dams and 777 DEGs in HFD dams. We found that genes related to snRNP binding and translation initiation were most significantly altered between the TMG and IMG. Although we were not able to discern a molecular mechanism, many small nuclear RNAs and small nucleolar RNAs were differentially expressed between the TMG and IMG responsible for cellular functions such as splicing and ribosome biogenesis, which provides and interesting avenue for future research. Our study supports the hypothesis that collection of the mammary gland from a particular location influences mammary gland gene expression, thereby highlighting the importance for researchers to be vigilant in documenting and reporting which mammary gland they are using for their studies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Diet, Fat-Restricted / adverse effects
  • Diet, High-Fat / adverse effects
  • Female
  • Gene Expression Regulation / genetics
  • Lactation / genetics*
  • Mammary Glands, Animal / metabolism*
  • Mice
  • RNA / genetics
  • Transcriptome / genetics*

Substances

  • RNA

Grants and funding

Dr. Wenli Li was supported by appropriated project 5090-31000-026-00-D from the USDA Agriculture Research Service (Dairy Forage Research Center). This research used resources provided by the SCINet project of the USDA Agricultural Research Service, ARS project number 0500-00093-001-00-D. Mention of trade names or commercial products in this article is solely for the purpose of providing specific information and does not imply recommendation by the US Department of Agriculture. The USDA is an equal opportunity provider and employer. Dr. Laura Hernandez and Adrienne Cheng were supported by Dr. Bob Aiello at Karos Pharmaceuticals, UW-Madison Graduate School Fall Competition MSN215653, and USDA-Hatch MSN158160.