A transcriptional network governing ceramide homeostasis establishes a cytokine-dependent developmental process

Ruiqi Liao, Abiola Babatunde, Stephanie Qiu, Hamsini Harikumar, Joshua J. Coon, Katherine A. Overmyer, Yusuf A. Hannun, Chiara Luberto and Emery H. Bresnick ()
Additional contact information
Ruiqi Liao: University of Wisconsin School of Medicine and Public Health
Abiola Babatunde: University of Wisconsin School of Medicine and Public Health
Stephanie Qiu: University of Wisconsin School of Medicine and Public Health
Hamsini Harikumar: University of Wisconsin School of Medicine and Public Health
Joshua J. Coon: University of Wisconsin School of Medicine and Public Health
Katherine A. Overmyer: University of Wisconsin School of Medicine and Public Health
Yusuf A. Hannun: Stony Book University
Chiara Luberto: Stony Brook University
Emery H. Bresnick: University of Wisconsin School of Medicine and Public Health

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Transcriptional mechanisms controlling developmental processes establish and maintain proteomic networks, which can govern the levels of intracellular small molecules. Although dynamic changes in bioactive small molecules can link transcription factor and genome activity with cell state transitions, many mechanistic questions are unresolved. Using quantitative lipidomics and multiomics, we discover that the hematopoietic transcription factor GATA1 establishes ceramide homeostasis during erythroid differentiation by regulating genes encoding sphingolipid metabolic enzymes. Inhibiting a GATA1-induced sphingolipid biosynthetic enzyme, delta(4)-desaturase, or disrupting ceramide homeostasis with cell-permeable dihydroceramide or ceramide is detrimental to erythroid, but not myeloid, progenitor activity. Coupled with genetic editing-based rewiring of the regulatory circuitry, we demonstrate that ceramide homeostasis commissions vital stem cell factor and erythropoietin signaling by opposing an inhibitory protein phosphatase 2A-dependent, dual-component mechanism. Integrating bioactive lipids as essential components of GATA factor mechanisms to control cell state transitions has implications for diverse cell and tissue types.

Date: 2023
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-42978-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42978-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-42978-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().