Year: 2025
Type: article
Study design: Observational Study
Abstract: Dynamic steady-state lineage contribution of human hematopoietic stem cell (HSC) clones needs to be assessed over time. However, clonal contribution of HSCs has only been investigated at single time points and without assessing the critical erythroid and platelet lineages. Here we screened for somatic mutations in healthy aged individuals, identifying expanded HSC clones accessible for lineage tracing of all major blood cell lineages. In addition to HSC clones with balanced contribution to all lineages, we identified clones with all myeloid lineages but no or few B and T lymphocytes or all myeloid lineages and B cells but no T cells. No other lineage restriction patterns were reproducibly observed. Retrospective phylogenetic inferences uncovered a 'hierarchical' pattern of descendant subclones more lineage biased than their ancestral clone and a more common 'stable' pattern with descendant subclones showing highly concordant lineage contributions with their ancestral clone, despite decades of separation. Prospective lineage tracing confirmed remarkable stability over years of HSC clones with distinct lineage replenishment patterns.
Source: Nature Genetics
Authors: Tetsuichi Yoshizato, Christer Nilsson, Francesca Grasso, Kari Högstrand, Stefania Mazzi, Axel Winroth, Madeleine Lehander, Indira Barbosa, Gunilla Waldin, Teresa Mortera-Blanco, Monika Jansson, Mikaela Hillberg Widfeldt, Affaf Aliouat, Margs S. Brennan, Ellen Markljung, Amy Hillen, Edwin Chari, Eva Hellström-Lindberg, Warren W. Kretzschmar, Petter S. Woll, Sten Eirik W. Jacobsen
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: Torsten Söderbergs Stiftelse, Cancerfonden, Karolinska Institutet, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet, Astellas Pharma, Mochida Memorial Foundation for Medical and Pharmaceutical Research, Radiumhemmets Forskningsfonder, Astellas Foundation for Research on Metabolic Disorders, Science for Life Laboratory, Dr Åke Olssons Stiftelse för Haematologisk Forskning, Medical Research Council, Center for Innovative Medicine, Tobias Foundation
OpenAlex ID: W4416102933