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FASN-dependent de novo lipogenesis is required for brain development

ABSTRACT: Fate and behaviour of neural progenitor cells is tightly regulated during mammalian brain development. Metabolic pathways, such as glycolysis and oxidative phosphorylation, that are required for supplying energy and providing molecular building blocks to generate cells, govern progenitor function. However, the role of de novo lipogenesis, which is the conversion of glucose into fatty acids through the multi-enzyme protein fatty acid synthase (FASN), for brain development remains unknown. Using Emx1Cre-mediated, tissue-specific deletion of Fasn in the mouse embryonic telencephalon, we show that loss of FASN causes severe microcephaly, largely due to altered polarity of apical, radial glia progenitors (APs) and reduced progenitor proliferation. Further, genetic deletion and pharmacological inhibition of FASN in human embryonic stem cell (ESC)-derived forebrain organoids identifies a conserved role of FASN-dependent lipogenesis for radial glia cell polarity and progenitor expansion in the developing human forebrain. Thus, our data establish a role of de novo lipogenesis for mouse and human brain development and identify a link between progenitor cell polarity and lipid metabolism.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Neuronal Stem Cell

SUBMITTER: Daniel Gonzalez

LAB HEAD: Sebastian Jessberger

PROVIDER: PXD026110 | Pride | 2022-01-14

REPOSITORIES: Pride

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			Action	DRS
	20210323_002_S285769_EtOH_500cells_DIA_Rep1_S2-A1_1_1500.d.zip	Other
	20210323_003_S285771_CER_24h_500cells_DIA_Rep1_S2-B1_1_1501.d.zip	Other
	20210323_005_S285771_CER_24h_500cells_DIA_Rep2_S2-B2_1_1503.d.zip	Other
	20210323_006_S285769_EtOH_500cells_DIA_Rep2_S2-A2_1_1504.d.zip	Other
	20210323_009_S285769_EtOH_500cells_DIA_Rep3_S2-A3_1_1507.d.zip	Other

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