瑞典卡罗林斯卡大学Sten Eirik W. Jacobsen小组研制了谱系限制干细胞对人类造血的稳定克隆贡献。2025年11月11日，国际知名学术期刊《自然—遗传学》发表了这一成果。

在这里，课题组人员筛选了健康老年人的体细胞突变，确定了扩展的HSC克隆，可用于所有主要血细胞谱系的谱系追踪。除了对所有谱系贡献均衡的HSC克隆外，研究组还鉴定了具有所有髓系但没有或很少有B和T淋巴细胞的克隆，或具有所有髓系和B细胞但没有T细胞的克隆。未观察到其他可重复的谱系限制模式。回顾性的系统发育推断揭示了后代亚克隆的“等级”模式比他们的祖先克隆更偏向于谱系，而更常见的“稳定”模式是后代亚克隆与他们的祖先克隆表现出高度一致的谱系贡献，尽管几十年的分离。前瞻性谱系追踪证实了多年来具有不同谱系补充模式的HSC克隆的显着稳定性。

研究人员表示，人类造血干细胞（HSC）克隆的动态稳态谱系贡献需要随着时间的推移进行评估。然而，造血干细胞的克隆贡献仅在单个时间点进行了研究，而没有评估关键的红细胞和血小板谱系。

附：英文原文

Title: Stable clonal contribution of lineage-restricted stem cells to human hematopoiesis

Author: Yoshizato, Tetsuichi, Nilsson, Christer, Grasso, Francesca, Hgstrand, Kari, Mazzi, Stefania, Winroth, Axel, Lehander, Madeleine, Barbosa, Indira, Waldin, Gunilla, Mortera-Blanco, Teresa, Jansson, Monika, Widfeldt, Mikaela Hillberg, Aliouat, Affaf, Brennan, Margs S., Markljung, Ellen, Hillen, Amy, Chari, Edwin, Hellstrm-Lindberg, Eva, Kretzschmar, Warren W., Woll, Petter S., Jacobsen, Sten Eirik W.

Issue&Volume: 2025-11-11

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.

DOI: 10.1038/s41588-025-02405-w

Source: https://www.nature.com/articles/s41588-025-02405-w