Jan-Eric Bökenkamp

Projects: SP-8: The causes of replication stress in response to whole chromosomal aneuploidy

Institutions: University of Kaiserslautern Department of Molecular Genetics

https://orcid.org/0000-0002-1662-0349
Alexander Wolff adminproject_administratorasset_housekeeperasset_gatekeeper

Projects: SP-Z: NGS-based approaches for systematic analysis of genomic and chromosome instability Bernd Wollnik, Göttingen, SP-5: Impaired chromosome integrity caused by mutations in members of the BTR complex

Institutions: University of Göttingen University Medical Center (UMG) Institute of Human Genetics

https://orcid.org/0000-0003-2262-9056
Xiaoxiao Zhang project_administrator

Projects: Test, SP-3: A statistical modeling approach to identify common triggers for replication stress and mitotic chromosome missegregation, SP-1: Deciphering signaling pathways that promote accurate chromosome segregation after replication stress, SP-2: Molecular mechanisms of replication stress-induced mitotic chromosome missegregation, SP-4: Centrosome integrity as a determinant of replication stress and mitotic dysfunction, SP-5: Impaired chromosome integrity caused by mutations in members of the BTR complex, SP-8: The causes of replication stress in response to whole chromosomal aneuploidy, SP-Z: NGS-based approaches for systematic analysis of genomic and chromosome instability Bernd Wollnik, Göttingen, SP9: Mutual impact of replication origin firing regulation and mitotic chromosome segregation

Institutions: University of Applied Sciences Koblenz

Single-cell transcription profiles in Bloom syndrome patients link BLM deficiency with altered condensin complex expression signatures

Abstract (Expand)

Bloom syndrome (BS) is an autosomal recessive disease clinically characterized by primary microcephaly, growth deficiency, immunodeficiency, and predisposition to cancer. It is mainly caused by biallelic … loss-of-function mutations in the BLM gene, which encodes the BLM helicase, acting in DNA replication and repair processes. Here, we describe the gene expression profiles of three BS fibroblast cell lines harboring causative, biallelic truncating mutations obtained by single-cell (sc) transcriptome analysis. We compared the scRNA transcription profiles from three BS patient cell lines to two age-matched wild-type controls and observed specific deregulation of gene sets related to the molecular processes characteristically affected in BS, such as mitosis, chromosome segregation, cell cycle regulation, and genomic instability. We also found specific upregulation of genes of the Fanconi anemia pathway, in particular FANCM, FANCD2, and FANCI, which encode known interaction partners of BLM. The significant deregulation of genes associated with inherited forms of primary microcephaly observed in our study might explain in part the molecular pathogenesis of microcephaly in BS, one of the main clinical characteristics in patients. Finally, our data provide first evidence of a novel link between BLM dysfunction and transcriptional changes in condensin complex I and II genes. Overall, our study provides novel insights into gene expression profiles in BS on a single-cell level, linking specific genes and pathways to BLM dysfunction.

Authors: Ipek Ilgin Gönenc, Alexander Wolff, Markus Räschle, Bernd Wollnik

Date Published: 1st Oct 2021

Publication Type: Journal

Powered by
 (v.1.17.1)
About FAIRDOM | Funding and Programmes | Credits
Copyright © 2008 - 2025 The University of Manchester and HITS gGmbH