美国波士顿丹娜-法波癌症研究中心R. Grant Rowe、Hojun Li研究组揭示了人一生中造血的动态变化。该项研究成果发表在2024年12月5日出版的《自然—方法学》上。

为了填补造血干细胞和祖细胞特性随年龄变化这一空白，研究人员分析了人类造血干细胞（HSCs）和祖细胞在妊娠期、成熟期和衰老期的单个转录组状态。

研究揭示出决定造血干细胞年龄特异性分化的基因表达网络，以及整个生命过程中命运决定和血系引物的动态变化。

此外，研究人员还发现并从功能上验证了胎儿特异性造血干细胞的状态，这种状态具有强大的移植和多谱系发育能力。此外，研究还观察到，根据已知的转录年龄状态对急性髓性白血病进行分类，研究发现生命早期转录程序的开启与不良预后有关。总之，该研究提供了干细胞与人类实时年龄变化相关疾病的框架。

据介绍，造血干细胞会随年龄变化调整血量输出，以维持与年龄相适应的生理学。在模式生物中，已观察到造血变化与具有明确年龄偏向的造血干细胞特征相对应。然而，仍不清楚造血干细胞和祖细胞的特性在人一生中是如何变化的。

附：英文原文

Title: The dynamics of hematopoiesis over the human lifespan

Author: Li, Hojun, Ct, Parker, Kuoch, Michael, Ezike, Jideofor, Frenis, Katie, Afanassiev, Anton, Greenstreet, Laura, Tanaka-Yano, Mayuri, Tarantino, Giuseppe, Zhang, Stephen, Whangbo, Jennifer, Butty, Vincent L., Moiso, Enrico, Falchetti, Marcelo, Lu, Kate, Connelly, Guinevere G., Morris, Vivian, Wang, Dahai, Chen, Antonia F., Bianchi, Giada, Daley, George Q., Garg, Salil, Liu, David, Chou, Stella T., Regev, Aviv, Lummertz da Rocha, Edroaldo, Schiebinger, Geoffrey, Rowe, R. Grant

Issue&Volume: 2024-12-05

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.

DOI: 10.1038/s41592-024-02495-0

Source: https://www.nature.com/articles/s41592-024-02495-0