Clonal memory of cell division in humans diverges between healthy haematopoiesis and acute myeloid leukaemia
Donada, A.; Hermange, G.; Tocci, T.; Midoun, A.; Prevedello, G.; Hadj Abed, L.; Dupre, D.; SUN, W.; Milo, I.; Tenreira Bento, S.; Pospori, C.; Innes, A.; Willekens, C.; Vargaftig, J.; Michonneau, D.; Lo Celso, C.; Servant, N.; Duffy, K.; Isambert, H.; Cournede, P.-H.; Laplane, L.; Perie, L.
Show abstract
Clonal memory, a cellular property inherited across at least two divisions, has emerged as a key driver of cell heterogeneity. To uncover its roles in human haematopoiesis, we developed 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 leukemic cells. Epigenetic remodelling using a bromodomain inhibitor partially restores the clonal memory in division in leukemic 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 new avenues for tuning cell heterogeneity in healthy and pathological tissues.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- LAG-3 blockade reactivates the CD8+ T cell expansion program to re-expand contracted clones in the tumor 97%
- A single-cell atlas of pig gastrulation as a resource for comparative embryology 97%
- Integration of scHi-C and scRNA-seq data defines distinct 3D-regulated and biological-context dependent cell subpopulations 97%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.