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A single-cell transcriptomic atlas of the periventricular proliferative zone in the late gestation fetal brain in the pigtail macaque.

Overview

Authors: John A Cornelius1, Megana Shivakumar1,2, Taeyun Kim1, Orlando Cervantes1,3, Raj P Kapur4,5, Hazel Huang1, Hong Zhao1, Briana M Del Rosario1, Amanda Li1,6, Richard J Li1,7, Sidney Sun1,4, Andrew E Vo1,8, Gygeria Manuel1,9, Akshaj Bharadwaj1, Jeff Munson10, Miranda Li8, Edmunda Li1, Sophia Chima1,3, Austyn Orvis11, Michelle Coleman11
and 19 other authorsAlexandra Christodolou12, Melissa R Berg12, Britni C Curtis12, Brenna A Menz12, Jin Dai12, Inah D Golez12, Solomon N Wangari12, Stephen A McCartney1, Kristen Noble13, Pilar Flores-Espinoza14, Addy Cecilia Helguera-Repetto15, Andrea Olmos-Ortiz15, Monica Selena Fonseca-Perez15, Chris English12, Audrey Baldessari12, Nardhy Gomez-Lopez16, Rebecca Hodge17, Lakshmi Rajagopal3,12,14, Kristina M Adams Waldorf1,3,13
ORCID iDs: Hong Zhao
17 affiliations
  1. Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, United States
  2. Pacific Northwest University of Health Sciences (PNWU) College of Osteopathic Medicine, Yakima, WA, United States
  3. Department of Global Health, University of Washington, Seattle, WA, United States
  4. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States
  5. Seattle Children's Hospital, Seattle, WA, United States
  6. Case Western Reserve University School of Medicine, Cleveland, OH, United States
  7. Columbia University, New York, NY, United States
  8. University of Washington School of Medicine, Seattle, WA, United States
  9. Morehouse School of Medicine, Atlanta, GA, United States
  10. Department of Psychiatry, University of Washington, Seattle, WA, United States
  11. Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, United States
  12. Washington National Biomedical Research Center, Seattle, WA, United States
  13. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States
  14. Department of Obstetrics and Gynecology, University of Texas Medical Branch Galveston, Galveston, TX, United States
  15. Department of Immunobiochemistry, National Institute of Perinatology, Mexico City, Mexico
  16. Departments of Obstetrics and Gynecology and Pathology and Immunology, Center for Reproductive Health Sciences, Washington University in St. Louis, St. Louis, MO, United States
  17. Allen Brain Institute, Seattle, WA, United States
Institutions: University of Washington (United States); Pacific Northwest University of Health Sciences (United States); Seattle Children's Hospital (United States); Case Western Reserve University (United States); Columbia University (United States); Morehouse School of Medicine (United States); Seattle Children's Research Institute (United States); Vanderbilt University Medical Center (United States); The University of Texas Medical Branch at Galveston (United States); Instituto Nacional de Perinatología (Mexico); Washington University in St. Louis (United States)
Journal: Frontiers in neuroscience, volume 20, article 1785001
Dates: received 10 January 2026; accepted 26 May 2026; published online 3 August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.3389/fnins.2026.1785001 · PMID 42609459 · PMCID PMC13478084 · OpenAlex W7172303358
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), human (organism), non-human primate (organism)
Methods: Statistics, Smoothing, state filtering, decompositions, Spectral & time-frequency, Connectivity
Keywords: astrocyte, brain, fetus, neuron, microglia, neurodevelopment, neuroprogenitor, nonhuman primate
Topic: Single-cell and spatial transcriptomics (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: NIAID NIH HHS (R01 AI143265, R01 AI152268, R01 AI184481, R01 AI176777, R01 AI133976, R01 AI164588, T32 AI007509, R01 AI145890); NICHD NIH HHS (R01 HD098713); NIH HHS (P51 OD010425, U42 OD011123)
Citations: not cited yet (Europe PMC); 87 references in the paper

Abstract

Background: The fetal brain undergoes rapid cellular and structural changes in late gestation, when waves of neurogenesis and gliogenesis shape cortical circuitry. The ventricular zone (VZ), subventricular zone (SVZ), periventricular white matter (PVWM), and deep white matter (DWM) are enriched in neuroprogenitor cells, newborn neurons, and interneurons, which are regions challenging to study in the third-trimester human fetal brain. The nonhuman primate (NHP) provides a powerful translational model to overcome this limitation, given its close similarity to human neurodevelopmental trajectories. The study objective was to construct a single-cell RNA-Seq (scRNA-Seq) atlas of the late-gestation fetal brain of the pigtail macaque (Macaca nemestrina), focusing on cells in the periventricular proliferative zone.

Methods: A sample of the lateral ventricular wall, subventricular zone, and overlying white/gray matter was dissociated into single cells and processed through 10X Genomics sequencing, SoupX removal of ambient RNA, empty droplet removal, doublet exclusion, and Seurat's pipeline which consists of aggregation, unsupervised clustering, and cluster annotation to create a single-cell RNA-Seq (scRNA-Seq) atlas. We also investigated developmental trajectories using scVelo and CellRank2.

Results: This analysis captured diverse populations of neuroprogenitors, newborn neurons, developing lineages of excitatory and inhibitory neurons, oligodendrocytes, astrocytes, epithelial and vascular cells.

Conclusions: Single-cell populations from the third-trimester nonhuman primate fetal brain are highly similar to those in the human fetus at the level of major lineages. This late-gestation single-cell atlas of the periventricular proliferative zone provides a unique reference for progenitor, neuronal, glial, vascular, and immune cell states during a critical window of primate neurodevelopment, enabling mechanistic interrogation of how inflammatory, infectious, or hypoxic insults disrupt vulnerable neurogenic niches.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

Other data links

Data availability statement

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/geo/ (GSE305531 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305531)). The data can be explored using the UCSC Cell Browser: https://cells-test.gi.ucsc.edu/?ds=nemestrina-fetal-svz.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 39 authors, 8 keywords, 3 funders, 87 references.

Cite

This paper

Cornelius, J. A., Shivakumar, M., Kim, T., Cervantes, O., Kapur, R. P., Huang, H., Zhao, H., Del Rosario, B. M., Li, A., Li, R. J., Sun, S., Vo, A. E., Manuel, G., Bharadwaj, A., Munson, J., Li, M., Li, E., Chima, S., Orvis, A., . . . Adams Waldorf, K. M. (2026). A single-cell transcriptomic atlas of the periventricular proliferative zone in the late gestation fetal brain in the pigtail macaque. Frontiers in neuroscience, 20, 1785001. https://doi.org/10.3389/fnins.2026.1785001

BibTeX

@article{cornelius2026single,
author = {Cornelius, John A and Shivakumar, Megana and Kim, Taeyun and Cervantes, Orlando and Kapur, Raj P and Huang, Hazel and Zhao, Hong and Del Rosario, Briana M and Li, Amanda and Li, Richard J and Sun, Sidney and Vo, Andrew E and Manuel, Gygeria and Bharadwaj, Akshaj and Munson, Jeff and Li, Miranda and Li, Edmunda and Chima, Sophia and Orvis, Austyn and Coleman, Michelle and Christodolou, Alexandra and Berg, Melissa R and Curtis, Britni C and Menz, Brenna A and Dai, Jin and Golez, Inah D and Wangari, Solomon N and McCartney, Stephen A and Noble, Kristen and Flores-Espinoza, Pilar and Helguera-Repetto, Addy Cecilia and Olmos-Ortiz, Andrea and Fonseca-Perez, Monica Selena and English, Chris and Baldessari, Audrey and Gomez-Lopez, Nardhy and Hodge, Rebecca and Rajagopal, Lakshmi and Adams Waldorf, Kristina M},
title = {{A single-cell transcriptomic atlas of the periventricular proliferative zone in the late gestation fetal brain in the pigtail macaque}},
journal = {Frontiers in neuroscience},
year = {2026},
month = aug,
volume = {20},
pages = {1785001},
publisher = {Frontiers Media SA},
issn = {1662-4548},
doi = {10.3389/fnins.2026.1785001},
url = {https://doi.org/10.3389/fnins.2026.1785001},
pmid = {42609459},
pmcid = {PMC13478084}
}

RIS

TY - JOUR
AU - Cornelius, John A
AU - Shivakumar, Megana
AU - Kim, Taeyun
AU - Cervantes, Orlando
AU - Kapur, Raj P
AU - Huang, Hazel
AU - Zhao, Hong
AU - Del Rosario, Briana M
AU - Li, Amanda
AU - Li, Richard J
AU - Sun, Sidney
AU - Vo, Andrew E
AU - Manuel, Gygeria
AU - Bharadwaj, Akshaj
AU - Munson, Jeff
AU - Li, Miranda
AU - Li, Edmunda
AU - Chima, Sophia
AU - Orvis, Austyn
AU - Coleman, Michelle
AU - Christodolou, Alexandra
AU - Berg, Melissa R
AU - Curtis, Britni C
AU - Menz, Brenna A
AU - Dai, Jin
AU - Golez, Inah D
AU - Wangari, Solomon N
AU - McCartney, Stephen A
AU - Noble, Kristen
AU - Flores-Espinoza, Pilar
AU - Helguera-Repetto, Addy Cecilia
AU - Olmos-Ortiz, Andrea
AU - Fonseca-Perez, Monica Selena
AU - English, Chris
AU - Baldessari, Audrey
AU - Gomez-Lopez, Nardhy
AU - Hodge, Rebecca
AU - Rajagopal, Lakshmi
AU - Adams Waldorf, Kristina M
TI - A single-cell transcriptomic atlas of the periventricular proliferative zone in the late gestation fetal brain in the pigtail macaque
T2 - Frontiers in neuroscience
J2 - Front Neurosci
PY - 2026
DA - 2026/08/03
VL - 20
SP - 1785001
SN - 1662-4548
PB - Frontiers Media SA
DO - 10.3389/fnins.2026.1785001
UR - https://doi.org/10.3389/fnins.2026.1785001
LA - en
ER -

CSL-JSON

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