Sptlc1 is essential for myeloid differentiation and hematopoietic homeostasis
UMass Chan Affiliations
Department of Molecular, Cell and Cancer BiologyDocument Type
Journal ArticlePublication Date
2019-11-26Keywords
Hematopoiesis and Stem CellsPhagocytes
Granulocytes
and Myelopoiesis
chimera organism
emergency service
hospital
fatty acids
homeostasis
mice
palmitic acid
proto-oncogene protein c-kit
serine
sphingolipids
stress
Cancer Biology
Cell Biology
Cellular and Molecular Physiology
Metadata
Show full item recordAbstract
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.Source
Blood Adv. 2019 Nov 26;3(22):3635-3649. doi: 10.1182/bloodadvances.2019000729. Link to article on publisher's site
DOI
10.1182/bloodadvances.2019000729Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41251PubMed ID
31751474Notes
Full author list omitted for brevity. For the full list of authors, see article.
Related Resources
Rights
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.ae974a485f413a2113503eed53cd6c53
10.1182/bloodadvances.2019000729