小柯机器人

美国加州大学E. Camilla Forsberg团队近期取得重要工作进展，他们发现一种来自造血干细胞的年龄进行性血小板分化途径，会导致血栓形成加剧。相关研究成果2024年5月14日在线发表于《细胞》杂志上。

据介绍，随着年龄的增长，血小板失调急剧增加，并导致心血管疾病，这已经成为老年人死亡的主要原因。

研究人员揭示了一种从造血干细胞到血小板的直接分化途径，该途径随着年龄的增长而逐渐增强。值得注意的是，衰老富集的血小板通路与包括红细胞生成在内的所有其他造血谱系脱钩，并作为一个额外的层与典型的血小板产生平行运作。这导致了两种分子和功能上不同的巨核细胞祖细胞群体。

年龄诱导的巨核细胞祖细胞在原位和移植时移植、扩增、恢复和重建血小板的能力大大增强，并在老年小鼠中产生额外的血小板群体。这两种共存的血小板池会导致与年龄相关的血小板增多，并在体内显著增加血栓形成。与典型的血小板群相比，衰老富集的血小板在功能上具有高反应性。

总之，这些发现揭示了基于干细胞的衰老是血小板失调和年龄诱导的血栓形成的机制。

附：英文原文

Title: An age-progressive platelet differentiation path from hematopoietic stem cells causes exacerbated thrombosis

Author: Donna M. Poscablo, Atesh K. Worthington, Stephanie Smith-Berdan, Marcel G.E. Rommel, Bryce A. Manso, Reheman Adili, Lydia Mok, Roman E. Reggiardo, Taylor Cool, Raana Mogharrab, Jenna Myers, Steven Dahmen, Paloma Medina, Anna E. Beaudin, Scott W. Boyer, Michael Holinstat, Vanessa D. Jonsson, E. Camilla Forsberg

Issue&Volume: 2024-05-14

Abstract: Platelet dysregulation is drastically increased with advanced age and contributes to making cardiovascular disorders the leading cause of death of elderly humans. Here, we reveal a direct differentiation pathway from hematopoietic stem cells into platelets that is progressively propagated upon aging. Remarkably, the aging-enriched platelet path is decoupled from all other hematopoietic lineages, including erythropoiesis, and operates as an additional layer in parallel with canonical platelet production. This results in two molecularly and functionally distinct populations of megakaryocyte progenitors. The age-induced megakaryocyte progenitors have a profoundly enhanced capacity to engraft, expand, restore, and reconstitute platelets in situ and upon transplantation and produce an additional platelet population in old mice. The two pools of co-existing platelets cause age-related thrombocytosis and dramatically increased thrombosis in vivo. Strikingly, aging-enriched platelets are functionally hyper-reactive compared with the canonical platelet populations. These findings reveal stem cell-based aging as a mechanism for platelet dysregulation and age-induced thrombosis.

DOI: 10.1016/j.cell.2024.04.018

Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00413-6