Metabolic atlas of early human cortex reveals glycolytic remodeling and pentose phosphate pathway control of cell fate transitions.
Overview
and 7 other authors
Weihong Ge1, Ryan L. Kan1, Madeline G. Andrews7, Maximilian Haeussler6, Michael F. Wells3,8, Heather R. Christofk1, Aparna Bhaduri1,9- Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
- These authors contributed equally
- Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
- Department of Medicine, Endocrinology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
- Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA
- Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA, USA
- School of Biological and Health Systems Engineering, Arizona State University, Phoenix, AZ, USA
- Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA
- Lead contact
Abstract
Cortical development involves rapid progenitor expansion and cell diversification supported by tightly regulated metabolic programs, yet these programs remain largely uncharacterized in human development. Here, we generated a metabolic atlas of the early human cortex using primary tissue and stem cell-derived cortical organoids. We observed dynamic changes in core metabolic functions, including an unexpected increase in glycolysis and pentose phosphate pathway (PPP) activity during late neurogenesis. Manipulation of glucose availability in cortical organoids altered cell-type composition, increasing outer radial glia (oRG) and inhibitory neuron populations. Pharmacological and genetic inhibition of PPP enzymes recapitulated these cell fate changes. Ribose was sufficient to rescue radial glia (RG) gene expression changes, revert organoid cell-type composition, and restore levels of ATP and hypotaurine. These data identify a critical role for the PPP in modulating RG cell fate specification and generate a resource for future exploration of additional metabolic pathways in human cortical development.
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
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Data
Datasets cited
- doi:10.17632/
yd6d2g8mkn.1 — at the source; found in “Data and code availability”
Data and code availability
scRNA-seq and snRNA-seq data generated in this study have been deposited in GEO under accession number GSE292425. Processed metabolomics, methylation, imaging quantification, and sequencing metadata are provided in the supplemental tables indicated in the manuscript. Additional information required to reanalyze the data is available from the lead contact upon request.
All of the metabolomics data from this study are available in the supplemental tables. Additionally, we have created a heatmap viewer for the visualization, subsetting, and interaction with this metabolomic data that can be found here: https://
Supplementary tables are available in Mendeley Data: https://
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
Versions
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Version 3, 28 September 2026
- Publisher: — → Cell Press
- Authors: added Aparna Bhaduri (0000-0003-4625-6899); removed Aparna Bhaduri
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, pages, dates, 27 authors, 9 keywords, 3 funders, 75 references, 54 RRIDs.
Cite
This paper
Mil, J., Soto, J. A., Krall, A. S., Peloggia, J., Frigui, S., Fong, O. S., Sathe, L., Matulionis, N., Day, F., Stiles, L., Montales, K. P., Azizad, D. J., Gonzalez, C. E., Fazzari, E., Li, M. X., Nano, P. R., Martija, A. A., Perez-Ramirez, C. A., Nguyen, C. V., . . . Bhaduri, A. (2026). Metabolic atlas of early human cortex reveals glycolytic remodeling and pentose phosphate pathway control of cell fate transitions. Cell, S0092-8674(26)00821-4. https://
BibTeX
@article{mil2026metaboli
author = {Mil, Jessenya and Soto, Jose A. and Krall, Abigail S. and Peloggia, Julia and Frigui, Sara and Fong, Olivia S. and Sathe, Laila and Matulionis, Nedas and Day, Francesca and Stiles, Linsey and Montales, Katrina P. and Azizad, Daria J. and Gonzalez, Carlos E. and Fazzari, Elisa and Li, Matthew X. and Nano, Patricia R. and Martija, Antoni A. and Perez-Ramirez, Cesar A. and Nguyen, Claudia V. and Wick, Brittney and Ge, Weihong and Kan, Ryan L. and Andrews, Madeline G. and Haeussler, Maximilian and Wells, Michael F. and Christofk, Heather R. and Bhaduri, Aparna},
title = {{Metabolic atlas of early human cortex reveals glycolytic remodeling and pentose phosphate pathway control of cell fate transitions}},
journal = {Cell},
year = {2026},
month = aug,
pages = {S0092--8674(26)00821--4
publisher = {Cell Press},
issn = {0092-8674},
doi = {10.1016/
url = {https://
pmid = {42551423},
pmcid = {PMC13537306}
}
RIS
TY - JOUR
AU - Mil, Jessenya
AU - Soto, Jose A.
AU - Krall, Abigail S.
AU - Peloggia, Julia
AU - Frigui, Sara
AU - Fong, Olivia S.
AU - Sathe, Laila
AU - Matulionis, Nedas
AU - Day, Francesca
AU - Stiles, Linsey
AU - Montales, Katrina P.
AU - Azizad, Daria J.
AU - Gonzalez, Carlos E.
AU - Fazzari, Elisa
AU - Li, Matthew X.
AU - Nano, Patricia R.
AU - Martija, Antoni A.
AU - Perez-Ramirez, Cesar A.
AU - Nguyen, Claudia V.
AU - Wick, Brittney
AU - Ge, Weihong
AU - Kan, Ryan L.
AU - Andrews, Madeline G.
AU - Haeussler, Maximilian
AU - Wells, Michael F.
AU - Christofk, Heather R.
AU - Bhaduri, Aparna
TI - Metabolic atlas of early human cortex reveals glycolytic remodeling and pentose phosphate pathway control of cell fate transitions
T2 - Cell
J2 - Cell
PY - 2026
DA - 2026/
SP - S0092
EP - 8674(26)00821-4
SN - 0092-8674
PB - Cell Press
DO - 10.1016/
UR - https://
LA - en
ER -
CSL-JSON
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