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Lookup NU author(s): Dr Gavin ClowryORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 The Author(s). The evolutionary expansion of the human neocortex relies on species-specific features of intermediate progenitor cells (IPCs), including enhanced proliferation and neuronal production. The transcriptomic differences in IPCs underlying their differential capacity across species remain elusive. To identify the transcriptional signature of human IPCs (hIPCs), we isolated TBR2-positive IPCs from developing human neocortex. A comparative genome-wide expression analysis of IPC transcriptional profiles from human and mouse outlined genes preferentially expressed in hIPCs encoding key factors of cell signaling, transcriptional regulation, and proliferation. Mutations in several hIPC-specific genes were linked to cortical malformations and brain tumors. Functional experiments involving hIPC-specific overexpression of CDKN3 in developing mouse cortex validated the pivotal role of CDKN3 in IPC proliferation and neurogenesis, and supported its identification as a key determinant of hIPC biogenesis. Our findings offer new insights into the molecular features of hIPCs underlying their capacity to mediate the evolutionary expansion of the human neocortex.
Author(s): Ulmke PA, Ivanov MN, Nguyen HD, Pham L, Muchamedin A, Alzu'bi A, Veleva LV, Kachovski T, Mao X, Lubieniecki KP, Kovachev E, Clowry GJ, Tonchev AB, Nguyen HP, Tuoc T
Publication type: Article
Publication status: Published
Journal: Stem Cell Reports
Year: 2026
Pages: Epub ahead of print
Online publication date: 09/07/2026
Acceptance date: 11/06/2026
Date deposited: 21/07/2026
ISSN (electronic): 2213-6711
Publisher: Cell Press
URL: https://doi.org/10.1016/j.stemcr.2026.103012
DOI: 10.1016/j.stemcr.2026.103012
Data Access Statement: RNA-seq data have been deposited in the NCBI Sequence Read Archive (SRA) under the BioProject accession number PRJNA1213291. This paper does not report original code. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.
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