Identification of a foetal epigenetic compartment in adult human kidney. Issue 3 (4th March 2022)

• Record Type: Journal Article
• Authors: Wiencke, John K.; Zhang, Ze; Koestler, Devin C.; Salas, Lucas A.; Molinaro, Annette M.; Christensen, Brock C.; Kelsey, Karl T.
• Is Part Of: Epigenetics. Volume 17:Issue 3(2022)
• Page Start: 335
• Page End: 355
• Publication Date: 2022-03-04
• Subjects: Kidney -- DNA methylation -- epigenetics -- foetal stem cells -- stem cell niche; Epigenesis -- Periodicals; Epigenetica; 572.86505
• DOI: 10.1080/15592294.2021.1900027
• Languages: English
• ISSNs: 1559-2294

Abstract

ABSTRACT: The mammalian kidney has extensive repair capacity; however, identifying adult renal stem cells has proven elusive. We applied an epigenetic marker of foetal cell origin (FCO) in diverse human tissues as a probe for developmental cell persistence, finding a 5.4-fold greater FCO proportion in kidney. Normal kidney FCO proportions averaged 49% with extensive interindividual variation. FCO proportions were significantly negatively correlated with immune-related gene expression and positively correlated with genes expressed in the renal medulla, including those involved in renal organogenesis (e.g., FGF2, PAX8, and HOXB7) . FCO associated genes also mapped to medullary nephron segments in mouse and rat, suggesting evolutionary conservation of this cellular compartment. Renal cancer patients whose tumours contained non-zero FCO scores survived longer. The kidney appears unique in possessing substantial foetal epigenetic features. Further study of FCO-related gene methylation may elucidate regenerative regulatory programmes in tissues without apparent discrete stem cell compartments.