Journal Article

DKFZ-2024-02226

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Analysis of population heterogeneity in CHO cells by genome-wide DNA methylation analysis and by multi-modal single-cell sequencing.

Böhl, E. (First author)DKFZ* ; Raddatz, G. (First author)DKFZ* ; Roy, S. ; Huang, L. ; Sandhu, J. K. ; Igwe, E. I. ; Rodríguez-Paredes, M.DKFZ* ; Böhl, F. ; Lyko, F. (Last author)DKFZ*

2024
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.jbiotec.2024.10.012

Abstract: CHO cells are major hosts for the industrial production of therapeutic proteins and their production stability is of considerable economic significance. It is widely known that CHO cells can rapidly acquire genetic alterations, which affects their genetic homogeneity over time. However, the role of non-genetic mechanisms, including epigenetic mechanisms such as DNA methylation, remains poorly understood. We have now used whole-genome bisulfite sequencing to establish single-base methylation maps of eight independent CHO cell lines. Our results identify CpG islands and low-methylated regions as conserved elements with dynamic DNA methylation. Interestingly, methylation patterns were found to cluster clearly along the three main branches of CHO evolution, with no directional changes over short culture periods. Furthermore, multi-ome single-cell sequencing of 9,833 nuclei from three independent cultures revealed dynamic subpopulation structures characterized by robust expression differences in pathways related to protein production. Our findings thus provide novel insights into the epigenetic landscape and heterogeneity of CHO cells and support the development of epigenetic biomarkers that trace the emergence of subpopulations in CHO cultures.

Keyword(s): CHO cells ; DNA methylation ; Epigenetics ; Evolution ; single-cell sequencing ; subpopulations

Note: #EA:A130#LA:A130# / 2024 Oct 31:396:72-79 / DKFZ-ZMBH Alliance

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Contributing Institute(s):

1. A130 Epigenetik (A130)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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