Single-cell chromatin accessibility landscape of T cell-mediated rejection and BK polyomavirus-associated nephropathy

Jingyi Zhou1,2,3,4,5, Hao Wu6,7,8, Qin Zhou1,2,3,4,5

  • 1Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Renal Failure
|July 9, 2025
PubMed

Insights

Single-cell ATAC sequencing reveals distinct chromatin landscapes in kidney transplant rejection (TCMR) and BK polyomavirus-associated nephropathy (BKPyVAN). This study identifies key cell populations and regulatory pathways, aiding in understanding these transplant complications.

Area of Science:

  • Nephrology
  • Immunology
  • Genomics

Background:

  • Kidney transplantation faces challenges from T cell-mediated rejection (TCMR) and BK polyomavirus-associated nephropathy (BKPyVAN).
  • Accurate diagnosis is crucial for timely intervention, but molecular understanding remains limited.
  • Developing novel diagnostic strategies requires deeper insights into the molecular underpinnings of these conditions.

Purpose of the Study:

  • To investigate the chromatin landscape of kidney samples with TCMR or BKPyVAN at the single-cell level.
  • To identify distinct cell population dynamics and chromatin changes associated with each condition.
  • To uncover upstream regulators of chromatin modifications in TCMR and BKPyVAN.

Main Methods:

  • Single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) was applied to kidney transplant samples.
  • Analysis focused on chromatin accessibility at the single-cell level.
  • Computational methods were used to identify cell populations, pathways, and regulatory elements.

Main Results:

  • scATAC-seq revealed distinct cell population dynamics in TCMR and BKPyVAN samples.
  • Enriched pathways associated with chromatin changes were identified for both conditions.
  • Upstream transcriptional and epigenetic regulators were analyzed for each cell population.

Conclusions:

  • This study provides a high-resolution view of the chromatin landscape in kidney transplant complications.
  • Findings offer valuable resources for characterizing the molecular features of TCMR and BKPyVAN.
  • The identified regulators shed light on molecular mechanisms underlying these transplant-related diseases.