Department of Molecular, Cell and Cancer Biology
Cancer Biology | Cell Biology | Cellular and Molecular Physiology
Serine palmitoyltransferase (SPT) long-chain base subunit 1 (SPTLC1) is 1 of the 2 main catalytic subunits of the SPT complex, which catalyzes the first and rate-limiting step of sphingolipid biosynthesis. Here, we show that Sptlc1 deletion in adult bone marrow (BM) cells results in defective myeloid differentiation. In chimeric mice from noncompetitive BM transplant assays, there was an expansion of the Lin- c-Kit+ Sca-1+ compartment due to increased multipotent progenitor production, but myeloid differentiation was severely compromised. We also show that defective biogenesis of sphingolipids in the endoplasmic reticulum (ER) leads to ER stress that affects myeloid differentiation. Furthermore, we demonstrate that transient accumulation of fatty acid, a substrate for sphingolipid biosynthesis, could be partially responsible for the ER stress. Independently, we find that ER stress in general, such as that induced by the chemical thapsigargin or the fatty acid palmitic acid, compromises myeloid differentiation in culture. These results identify perturbed sphingolipid metabolism as a source of ER stress, which may produce diverse pathological effects related to differential cell-type sensitivity.
Hematopoiesis and Stem Cells, Phagocytes, Granulocytes, and Myelopoiesis, chimera organism, emergency service, hospital, fatty acids, homeostasis, mice, palmitic acid, proto-oncogene protein c-kit, serine, sphingolipids, stress
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Copyright The American Society of Hematology. Publisher PDF posted as allowed by the publisher's copyright and author rights information at https://ashpublications.org/bloodadvances/pages/copyright.
DOI of Published Version
Blood Adv. 2019 Nov 26;3(22):3635-3649. doi: 10.1182/bloodadvances.2019000729. Link to article on publisher's site
Parthibane V, Acharya U, Acharya JK. (2019). Sptlc1 is essential for myeloid differentiation and hematopoietic homeostasis. Open Access Publications by UMass Chan Authors. https://doi.org/10.1182/bloodadvances.2019000729. Retrieved from https://escholarship.umassmed.edu/oapubs/4037