Sphingolipids in Hematopoiesis: Exploring Their Role in Lineage Commitment

Abstract

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.

Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies

“…Furthermore, S1PR 3 gene expression was elevated in AML patient samples compared to subjects without AML further pointing to a role for S1PR 3 as a potential leukemogenic factor [ 182 ]. However, this finding seems to oppose other studies which came to different conclusions [ 129 , 183 , 184 ]. First, S1PR 3 expression was shown to be very low in normal hematopoietic stem and progenitor cells (HSPCs) and to be highest in mature myeloid cells, hinting to a potential role for S1PR 3 in assisting myeloid differentiation.…”

“…While the discovery of the roles of SLs as bioactive molecules in hematological malignancies dates back to the 1980s, experimental evidence of their complex roles in normal hematopoiesis has been uncovered more recently [ 129 ]. As hematological malignancies often rise due to aberrations in the process of normal hematopoiesis and hematopoietic differentiation, these recent advances linking SLs and lineage commitment provide a conceptual framework for a better understanding of the various effects of SLs also in hematological malignancies.…”

Insight and Recent Advances into the Role of Topography on the Cell Differentiation and Proliferation on Biopolymeric Surfaces

“…properties like hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs) and neu ral stem cells (NSCs). Furthermore, while HSCs can differentiate into all types of blood cells such as lymphoid cells (natural killer cells, B-and T-lymphocytes) and myeloid cells (erythrocytes, platelets, neutrophils, basophils, eosinophils, monocytes and macrophages [95], MSCs have the capacity to differentiate into connective tissue cell types [91,96] (oste ocytes, adipocytes, chondrogenic cell lineages) (Figure 3) [91]. Furthermore, there are two broad types of stem cells according to their developmen tal stage: Embryonic stem cells (ESCs) and adult stem cells (ASCs) [87].…”

Unexpected Amanita phalloides-Induced Hematotoxicity—Results from a Retrospective Study

“…The decreases in leukocytes and platelets suggest that the hematotoxicity may be due to a direct effect of the toxin on the bone marrow [ 32 ]. Hematopoietic stem cells in the bone marrow differentiate into myeloid and lymphoid progenitor cells [ 33 , 34 ]. Myeloid progenitor cells differentiate into platelets, granulocytes, erythrocytes, or monocytes in the blood, while lymphoid progenitor cells differentiate into different subsets of lymphocytes and natural killer cells [ 33 ].…”

“…Hematopoietic stem cells in the bone marrow differentiate into myeloid and lymphoid progenitor cells [ 33 , 34 ]. Myeloid progenitor cells differentiate into platelets, granulocytes, erythrocytes, or monocytes in the blood, while lymphoid progenitor cells differentiate into different subsets of lymphocytes and natural killer cells [ 33 ]. Because of the observed effect on erythrocytes and platelets, α-amanitin appears to mainly affect myeloid progenitor cells.…”