Journal Article

DKFZ-2024-01148

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cell-type-specific consequences of mosaic structural variants in hematopoietic stem and progenitor cells.

Grimes, K. ; Jeong, H. ; Amoah, A. ; Xu, N. ; Niemann, J. ; Raeder, B. ; Hasenfeld, P. ; Stober, C. ; Rausch, T.DKFZ* ; Benito, E. ; Jann, J.-C. ; Nowak, D. ; Emini, R. ; Hoenicka, M. ; Liebold, A. ; Ho, A. ; Shuai, S. ; Geiger, H. ; Sanders, A. D. ; Korbel, J. (Last author)DKFZ*

2024
Macmillan Publishers Limited, part of Springer Nature London

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Please use a persistent id in citations: doi:10.1038/s41588-024-01754-2

Abstract: The functional impact and cellular context of mosaic structural variants (mSVs) in normal tissues is understudied. Utilizing Strand-seq, we sequenced 1,133 single-cell genomes from 19 human donors of increasing age, and discovered the heterogeneous mSV landscapes of hematopoietic stem and progenitor cells. While mSVs are continuously acquired throughout life, expanded subclones in our cohort are confined to individuals >60. Cells already harboring mSVs are more likely to acquire additional somatic structural variants, including megabase-scale segmental aneuploidies. Capitalizing on comprehensive single-cell micrococcal nuclease digestion with sequencing reference data, we conducted high-resolution cell-typing for eight hematopoietic stem and progenitor cells. Clonally expanded mSVs disrupt normal cellular function by dysregulating diverse cellular pathways, and enriching for myeloid progenitors. Our findings underscore the contribution of mSVs to the cellular and molecular phenotypes associated with the aging hematopoietic system, and establish a foundation for deciphering the molecular links between mSVs, aging and disease susceptibility in normal tissues.

Note: #LA:B480# / 2024 Jun;56(6):1134-1146

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Contributing Institute(s):

1. Mechanismen der genetischen Variation und Datenwissenschaft (B480)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 30 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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