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Sex differences in transcriptomic profiles in aged kidney cells of renin lineage

Yuliang Wang1,2, Diana G Eng3, Jeffrey W Pippin3

  • 1Paul G. Allen School of Computer Science and Engineering, University of Washington, Seattle, WA 98109, USA.

Aging
|April 21, 2018
PubMed

Insights

Aging kidney cells of renin lineage (CoRL) show significant gene expression changes, with distinct differences observed between male and female mice, highlighting sex-specific aging processes.

Area of Science:

  • Nephrology
  • Gerontology
  • Genomics

Background:

  • Renin-expressing cells in the kidney juxtaglomerular compartment (cells of renin lineage, CoRL) are potential progenitors for adult glomerular cells during disease.
  • CoRL numbers decline with age, and their responsiveness to stimuli like ACE-inhibition decreases, but the underlying mechanisms and sex-specific differences are unknown.

Purpose of the Study:

  • To investigate the impact of age and sex on the transcriptomic profiles of CoRL.
  • To identify age- and sex-related changes in gene expression and pathways within CoRL.

Main Methods:

  • Reporter mice (Ren1cCre|ZsGreen) were used to isolate and label CoRL from young (2 months) and aged (27 months) male and female mice.
  • Transcriptomic profiles of sorted CoRL were analyzed using RNA sequencing (RNA-seq).
  • Differential gene expression (DEG) analysis and gene ontology analysis were performed.

Main Results:

  • Aged CoRL exhibited 48 differentially expressed genes (DEGs) when both sexes were combined compared to young mice.
  • Sex-specific analysis revealed substantial differences: 159 DEGs in aged females and 503 DEGs in aged males compared to their young sex-matched counterparts.
  • Gene ontology analysis indicated major sex-dependent pathway alterations, with most DEGs changing in opposite directions or not significantly in the other sex.

Conclusions:

  • Advanced age induces significant changes in CoRL gene expression and ontology.
  • These age-related changes are markedly different between male and female mice, underscoring the importance of sex as a biological variable in kidney aging.
  • The findings highlight sex-specific molecular mechanisms underlying kidney aging in CoRL.
Keywords:
RNAseqdifferentially expressed genesgene ontologyglomeruluspodocyte

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