Liu Suying, Adams Sarah E, Zheng Haotian, Ehnot Juliana, Jung Seul K, Jeffrey Greer, Menna Theresa, Purton Louise, Lee Hongzhe, Kurre Peter
Comprehensive Bone Marrow Failure Center, Children's Hospital of Philadelphia, Philadelphia, United States.
Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States.
Elife. 2024 Dec 5;13:RP97504. doi: 10.7554/eLife.97504.
Hematopoietic dysfunction has been associated with a reduction in the number of active precursors. However, precursor quantification at homeostasis and under diseased conditions is constrained by the scarcity of available methods. To address this issue, we optimized a method for quantifying a wide range of hematopoietic precursors. Assuming the random induction of a stable label in precursors following a binomial distribution, estimates depend on the inverse correlation between precursor numbers and the variance of precursor labeling among independent samples. Experimentally validated to cover the full dynamic range of hematopoietic precursors in mice (1-10), we utilized this approach to demonstrate that thousands of precursors, which emerge after modest expansion during fetal-to-adult transition, contribute to native and perturbed hematopoiesis. We further estimated the number of precursors in a mouse model of Fanconi Anemia, showcasing how repopulation deficits can be classified as autologous (cell proliferation) and non-autologous (lack of precursor). Our results support an accessible and reliable approach for precursor quantification, emphasizing the contemporary perspective that native hematopoiesis is highly polyclonal.
造血功能障碍与活性前体细胞数量的减少有关。然而，在稳态和疾病状态下对前体细胞进行定量受到可用方法稀缺的限制。为了解决这个问题，我们优化了一种用于量化多种造血前体细胞的方法。假设前体细胞中稳定标记的随机诱导遵循二项分布，估计值取决于前体细胞数量与独立样本之间前体细胞标记方差的负相关。经过实验验证，该方法涵盖了小鼠造血前体细胞的整个动态范围（1 - 10），我们利用这种方法证明，在从胎儿到成人的过渡过程中适度扩增后出现的数千个前体细胞，对天然和受干扰的造血过程都有贡献。我们进一步估计了范可尼贫血小鼠模型中的前体细胞数量，展示了如何将再填充缺陷分为自体（细胞增殖）和非自体（前体细胞缺乏）。我们的结果支持一种可及且可靠的前体细胞定量方法，强调了天然造血是高度多克隆的这一当代观点。
