Multicellular organisms consist of different cell types that emerge in response to instructive signals. New evidence suggests that lipid composition modulates cell response to signalling cues. Here we propose that cell variability in lipid composition assists the divergence of differentiation trajectories, leading to the establishment of several cell identities.
This is a preview of subscription content, access via your institution
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 per month
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Get just this article for as long as you need it
Prices may be subject to local taxes which are calculated during checkout
Kramer, B. A., Sarabia Del Castillo, J. & Pelkmans, L. Multimodal perception links cellular state to decision-making in single cells. Science 377, 642–648 (2022).
Harayama, T. & Riezman, H. Understanding the diversity of membrane lipid composition. Nat. Rev. Mol. Cell Biol. 19, 281–296 (2018).
Levental, I. & Lyman, E. Regulation of membrane protein structure and function by their lipid nano-environment. Nat. Rev. Mol. Cell Biol. https://doi.org/10.1038/s41580-022-00524-4 (2022).
D’Angelo, G., Capasso, S., Sticco, L. & Russo, D. Glycosphingolipids: synthesis and functions. FEBS J. 280, 6338–6353 (2013).
Rappez, L. et al. SpaceM reveals metabolic states of single cells. Nat. Methods 18, 799–805 (2021).
Capolupo, L. et al. Sphingolipids control dermal fibroblast heterogeneity. Science 376, eabh1623 (2022).
Bhaduri, A., Neumann, E. K., Kriegstein, A. R. & Sweedler, J. V. Identification of lipid heterogeneity and diversity in the developing human brain. JACS Au. 1, 2261–2270 (2021).
Bien, T., Koerfer, K., Schwenzfeier, J., Dreisewerd, K. & Soltwisch, J. Mass spectrometry imaging to explore molecular heterogeneity in cell culture. Proc. Natl Acad. Sci. USA 119, e2114365119 (2022).
Frechin, M. et al. Cell-intrinsic adaptation of lipid composition to local crowding drives social behaviour. Nature 523, 88–91 (2015).
Russo, D. et al. Glycosphingolipid metabolic reprogramming drives neural differentiation. EMBO J. 37, e97674 (2018).
We thank P. Gönczy for critically reading the manuscript.
The authors declare no competing interests.
Rights and permissions
About this article
Cite this article
D’Angelo, G., La Manno, G. The lipotype hypothesis. Nat Rev Mol Cell Biol 24, 1–2 (2023). https://doi.org/10.1038/s41580-022-00556-w