Clonal memory of cell division in humans diverges between healthy haematopoiesis and acute myeloid leukaemia

Clonal memory, a cellular property inherited across at least two divisions, is a key driver of cell heterogeneity. To uncover its roles in human haematopoiesis, we develop high-resolution ex vivo tools that track both division and fate commitment of individual primary human haematopoietic stem and progenitor cells (HSPCs). We show that human HSPCs display a clonal memory of division, as cells descending from the same ancestor cell divide synchronously over multiple generations. In parallel, HSPCs inherit a clonal memory of fate commitment, independently of lineage identity. Both forms of clonal memory persist over at least two divisions, across different HSPC commitment stages and cell culture conditions. In contrast, malignant haematopoiesis exhibits lower synchronicity, revealing a disruption of clonal memory in leukaemic cells. Epigenetic remodelling using a bromodomain inhibitor partially restores the clonal memory in division in leukaemic HSPCs, highlighting the plasticity of this trait and its potential for therapeutic modulation. Our findings position clonal memory as a key regulator of human haematopoietic stem cell behaviour. Demonstrating that clonal memory can be modulated opens avenues for tuning cell heterogeneity in healthy and pathological tissues. Healthy blood stem and progenitor cells display synchronised division across generations — a form of clonal memory lost in AML. A bromodomain inhibitor partially restores it, revealing a potential epigenetic vulnerability in leukaemia.

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Publication Details

Journal
Nature Communications
Published
2026-07-28
DOI
https://doi.org/10.1038/s41467-026-75250-y
Primary Topic
Computational Drug Discovery Methods
Type
article
Field-Weighted Citation Impact
0.00

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article

Clonal memory of cell division in humans diverges between healthy haematopoiesis and acute myeloid leukaemia

Adil Midoun, Jacques Vargaftig, Christophe Willekens, Giulio Prevedello et al.
1 links
Nature Communications
Computational Drug Discovery Methods
article

Clonal memory of cell division in humans diverges between healthy haematopoiesis and acute myeloid leukaemia

Adil Midoun, Jacques Vargaftig, Christophe Willekens, Giulio Prevedello, Gurvan Hermange, Andrew J. Innes, Alessandro Donada, Lucie Laplane, Louisa Hadj Abed, Tiziana Tocci, Ken R. Duffy, David Michonneau, Nicolas Servant, Paul-Henry Cournède, Leïla Perié, Sabrina Tenreira Bento, Idan Milo, Wenjie Sun, Cristina Lo Celso, Constandina Pospori, Hervé Isambert, Délia Dupré
article en

Abstract

Clonal memory, a cellular property inherited across at least two divisions, is a key driver of cell heterogeneity. To uncover its roles in human haematopoiesis, we develop high-resolution ex vivo tools that track both division and fate commitment of individual primary human haematopoietic stem and progenitor cells (HSPCs). We show that human HSPCs display a clonal memory of division, as cells descending from the same ancestor cell divide synchronously over multiple generations. In parallel, HSPCs inherit a clonal memory of fate commitment, independently of lineage identity. Both forms of clonal memory persist over at least two divisions, across different HSPC commitment stages and cell culture conditions. In contrast, malignant haematopoiesis exhibits lower synchronicity, revealing a disruption of clonal memory in leukaemic cells. Epigenetic remodelling using a bromodomain inhibitor partially restores the clonal memory in division in leukaemic HSPCs, highlighting the plasticity of this trait and its potential for therapeutic modulation. Our findings position clonal memory as a key regulator of human haematopoietic stem cell behaviour. Demonstrating that clonal memory can be modulated opens avenues for tuning cell heterogeneity in healthy and pathological tissues. Healthy blood stem and progenitor cells display synchronised division across generations — a form of clonal memory lost in AML. A bromodomain inhibitor partially restores it, revealing a potential epigenetic vulnerability in leukaemia.

Nature Communications
Ikerbasque (ES), Northeastern University (US), Centre National de la Recherche Scientifique (FR), Imperial College Healthcare NHS Trust (GB), Inserm (FR), Université Paris Cité (FR), Université Paris Sciences et Lettres (FR), Université Paris-Saclay (FR), The Francis Crick Institute (GB), Hammersmith Hospital (GB), Institut Gustave Roussy (FR), Sorbonne Université (FR), Assistance Publique – Hôpitaux de Paris (FR), CentraleSupélec (FR), Centro Ricerche Enrico Fermi (IT), NIHR Imperial Biomedical Research Centre (GB), Institut d'Histoire et de Philosophie des Sciences et des Techniques (FR), Laboratoire d'études sur les monothéismes (FR), Sony (France) (FR), Hôpital Saint-Louis (FR), Physique des Cellules et Cancers (FR), Imperial College London (GB), Université Paris 1 Panthéon-Sorbonne (FR), Institut Curie (FR)
European Commission, Agence Nationale de la Recherche, Fondation de France, Institut National Du Cancer, Labex CelTisPhyBio
Openalex Percentile: Top 97%
Computational Drug Discovery Methods
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