Sapienza at the forefront of human genome research
2025 represents a turning point for European genomics.
Sapienza has led three internationally significant projects that together are reshaping the landscape of chromosome biology, genomic evolution and high-resolution functional genomics. The three studies trace a single thread that led to the sequencing of the genome of a particular human diploid cell line, commonly used as a reference model in the study of drugs and genetic diseases.
Until now, there was no specific reference genome for cell lines that would allow accurate analysis in complex regions. In a study published in Nature Communications last September, researchers at Sapienza University's Giunta Lab reconstructed the diploid reference genome of the RPE-1 cell line in its entirety, for the first time in a single European laboratory.
Derived from a non-cancerous human retinal pigment epithelial (RPE) cell, RPE-1 is one of the most widely used cell lines in experimental research, often serving as a key model. Furthermore, as a diploid cell line, the RPE-1 genome contains both maternal and paternal centromeres. This is the first time in the world that a human diploid cell line, widely used in research, has its own reference genome. This achievement places the new assembly, RPE1v1.1, among a very select group of diploid genomes, with each chromosome reconstructed in a single continuous sequence, obtained globally to date.
In this study, the Laboratory showed how many differences there are at the genetic level, not only between individuals but also within the same genome between maternal and paternal haplotypes, with peaks well above the expected 0.1% but over 6% divergence, revealing that we are not really “99.9% identical” but that in some regions, our DNA varies more than previously thought.
One of these hyper-variable regions is the centromere. Considered for decades to be the “black boxes” of the genome, they are the structure of the cell that holds together copies of a chromosome during cell division.
In a paper published in Science last July, the Laboratory demonstrated that the architecture of centromeres in humans and primates remains the same even when the DNA sequence changes radically. This discovery provided a crucial tool for analysing centromeres and validating the accuracy of the reference genome assembly to be used as a model for analysing sequencing data generated from the same cell line.
Finally, Giunta Lab was able to define for the first time a functional map of the human kinetochore, the complex protein structure found on the centromere of each chromatid, the part of the chromosome where the two sister chromatids are joined.
In the study published in Nature Communications last week, it was discovered that each chromosome has a kinetochore with a unique extension and position, which are not uniform among the 23 chromosomes, and that the two haplogroups (maternal and paternal) also differ from each other in the structure of the kinetochore, revealing a complexity that was previously impossible to observe.
‘These three studies demonstrate that cell line-specific reference genomes are a prerequisite for accurate functional genomics,’ says Simona Giunta, professor of Genome Evolution at Sapienza University and coordinator of GiuntaLab. ‘To understand the human genome, we therefore need to take an integrated view: evolution, structure and function. Finally, Giunta explains, this research paves the way for the complete assembly of the genomes of other cell lines to better understand the mutations or genetic variants related to diseases in all individuals.’
References:
Chromosome-specific centromeric patterns define the centeny map of the human genome -
Luca Corda and Simona Giunta – Science (2025) https://www.science.org/doi/10.1126/science.ads3484
The reference genome of the human diploid cell line RPE-1 - Emilia Volpe, Alessio Colantoni, Luca Corda, Elena Di Tommaso, Franca Pelliccia, Riccardo Ottalevi, Andrea Guarracino, Danilo Licastro, Luigi Faino, Mattia Capulli, Giulio Formenti, Evelyne Tassone & Simona Giunta - Nature Communications (2025)
https://www.nature.com/articles/s41467-025-62428-z
Cell line-matched reference enables high-precision functional genomics
Luca Corda, Emilia Volpe, Hamza Dallali, Elena Di Tommaso, Alessio Colantoni, Andrea Guarracino, Sai Swaroop Chittoor, Mattia Capulli, Evelyne Tassone & Simona Giunta- - Nature Communications (2025)
https://www.nature.com/articles/s41467-025-66155-3
Further Information
Simona Giunta – Department of Biology and Biotechnology Charles Darwin
https://sites.google.com/uniroma1.it/giuntalab/