2024-12-05 カリフォルニア大学サンディエゴ校(UCSD)
<関連情報>
- https://today.ucsd.edu/story/changes-in-blood-cell-production-over-the-lifetime-could-impact-leukemia-outcomes
- https://www.nature.com/articles/s41592-024-02495-0
ヒトの生涯にわたる造血のダイナミクス The dynamics of hematopoiesis over the human lifespan
Hojun Li,Parker Côté,Michael Kuoch,Jideofor Ezike,Katie Frenis,Anton Afanassiev,Laura Greenstreet,Mayuri Tanaka-Yano,Giuseppe Tarantino,Stephen Zhang,Jennifer Whangbo,Vincent L. Butty,Enrico Moiso,Marcelo Falchetti,Kate Lu,Guinevere G. Connelly,Vivian Morris,Dahai Wang,Antonia F. Chen,Giada Bianchi,George Q. Daley,Salil Garg,David Liu,Stella T. Chou,… R. Grant Rowe
Nature Methods Published:05 December 2024
DOI:https://doi.org/10.1038/s41592-024-02495-0
Abstract
Over a lifetime, hematopoietic stem cells (HSCs) adjust their lineage output to support age-aligned physiology. In model organisms, stereotypic waves of hematopoiesis have been observed corresponding to defined age-biased HSC hallmarks. However, how the properties of hematopoietic stem and progenitor cells change over the human lifespan remains unclear. To address this gap, we profiled individual transcriptome states of human hematopoietic stem and progenitor cells spanning gestation, maturation and aging. Here we define the gene expression networks dictating age-specific differentiation of HSCs and the dynamics of fate decisions and lineage priming throughout life. We additionally identifiy and functionally validate a fetal-specific HSC state with robust engraftment and multilineage capacity. Furthermore, we observe that classification of acute myeloid leukemia against defined transcriptional age states demonstrates that utilization of early life transcriptional programs associates with poor prognosis. Overall, we provide a disease-relevant framework for heterochronic orientation of stem cell ontogeny along the real time axis of the human lifespan.
