Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA.
Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
Cells. 2021 Sep 22;10(10):2507. doi: 10.3390/cells10102507.
Sphingolipids, associated enzymes, and the sphingolipid pathway are implicated in complex, multifaceted roles impacting several cell functions, such as cellular homeostasis, apoptosis, cell differentiation, and more through intrinsic and autocrine/paracrine mechanisms. Given this broad range of functions, it comes as no surprise that a large body of evidence points to important functions of sphingolipids in hematopoiesis. As the understanding of the processes that regulate hematopoiesis and of the specific characteristics that define each type of hematopoietic cells is being continuously refined, the understanding of the roles of sphingolipid metabolism in hematopoietic lineage commitment is also evolving. Recent findings indicate that sphingolipid alterations can modulate lineage commitment from stem cells all the way to megakaryocytic, erythroid, myeloid, and lymphoid cells. For instance, recent evidence points to the ability of de novo sphingolipids to regulate the stemness of hematopoietic stem cells while a substantial body of literature implicates various sphingolipids in specialized terminal differentiation, such as thrombopoiesis. This review provides a comprehensive discussion focused on the mechanisms that link sphingolipids to the commitment of hematopoietic cells to the different lineages, also highlighting yet to be resolved questions.
鞘脂类、相关酶和鞘脂代谢途径与多种细胞功能有关，通过内在和自分泌/旁分泌机制影响细胞稳态、细胞凋亡、细胞分化等复杂的多方面作用。鉴于鞘脂类具有广泛的功能，鞘脂类在造血中的重要作用有大量证据也就不足为奇了。随着对调节造血过程以及定义每种造血细胞的特定特征的理解不断得到完善，对鞘脂代谢在造血谱系分化中的作用的理解也在不断发展。最近的研究结果表明，鞘脂的改变可以调节从干细胞到巨核细胞、红细胞、髓系和淋巴系细胞的谱系分化。例如，最近的证据表明，从头合成的鞘脂可以调节造血干细胞的干性，而大量文献表明各种鞘脂参与特定的终末分化，如血小板生成。这篇综述提供了一个全面的讨论，重点讨论了鞘脂与造血细胞向不同谱系分化的机制，同时也强调了尚未解决的问题。
