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, Aviv Regev, Edroaldo Lummertz da Rocha, Geoffrey Schiebinger, R Grant Rowe

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. [email protected] of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. [email protected]. · pubmed

Paper

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.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper is relevant to longevity research as it investigates the dynamics of hematopoiesis and the properties of hematopoietic stem cells (HSCs) throughout the human lifespan, which can provide insights into age-related changes in stem cell function and their implications for aging and age-related diseases. The findings regarding the fetal-specific HSC state and its association with acute myeloid leukemia prognosis contribute to understanding the underlying mechanisms of aging and potential interventions. However, while the research presents important findings, it does not propose direct solutions for lifespan extension or the root causes of aging, limiting its overall impact to a score of 5.

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