[Sep. 24] 129th IRCMS Seminar

August 22 2025

We would like to inform you that the 129th IRCMS seminar has been scheduled as below.
* This IRCMS seminar is open to everyone.

Date      : September 24, 2025 (Wednesday)

Time      : 11:00-12:00

ZOOM　: Meeting ID: 923 6926 1737
            　 Passcode: Sem24Sep

Speaker : Dr. Stamatis Papathanasiou (Institute of Molecular Biology, Germany)

Title        : Errors in mitosis as a novel source of inherited (epi)genetic instability

Abstract:

One of the holy grails in cancer biology is to understand how genomic instability, a hallmark source of mutagenesis, arises. However, surprisingly little is known about non-genetic drivers of tumorigenesis.

We recently proposed a new model of transgenerational epigenetic instability caused by an initial incident of chromosome mis-segregation in mitosis. Specifically, we discovered a previously unappreciated phenomenon of heritable chromatin and transcriptional defects mediated by micronuclei (MN), which represent common features of nuclear atypia with central role in cancer development. These alterations are inherited after MN reincorporate into the normal nuclear environment of daughter cells and are strongly associated with long-lived DNA damage. We termed these structures of reincorporated MN chromosomes with altered chromatin "MN-bodies". We showed that chromosomal instability is inherently coupled to variation in gene expression, which may impact tumor evolution by a variety of mechanisms. This provided significant insight into the elusive mechanisms leading to non-genetic, cell-to-cell epigenetic variability observed in pathophysiology.

We are currently investigating under what exact circumstances cell division errors can generate chromatin state alterations, their inheritance in the progeny, and their functional significance, by developing novel single-cell based sequencing technologies and appropriate cell biology tools. Unravelling the functional properties of abnormal genomes at the single-cell level is fundamental for the understanding of cellular heterogeneity in disease and for the development of new therapeutic strategies.

2-3 major papers:

1. ^#Papathanasiou S, Mynhier NA, Liu S, Brunette G, Stokasimov E, Jacob E, Li L, Comenho C, van Steensel B, Buenrostro JD, ^#Zhang C-Z, ^#Pellman D. Transgenerational transcriptional heterogeneity from cytoplasmic chromatin. Article in Nature, doi: 10.1038/s41586-023-06157-7 (2022).  ^#co-corresponding authors

 2. Papathanasiou S, Markoulaki S, Blaine L, Leibowitz M, Zhang CZ, ^#Jaenisch R, ^#Pellman D. Whole chromosome loss and genomic instability in mouse embryos after CRISPR-Cas9 genome editing. Article in Nature Communications 12, 5855 (2021).

3. *Leibowitz M, *Papathanasiou S, Doerfler P, Blaine L, Sun L, Yao Y, Zhang CZ, Weiss M, Pellman D. Chromothripsis as an on-target consequence of CRISPR-Cas9 genome editing. Article in Nature Genetics 53, 895-905 (2021).  *equal contribution

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