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Identification of novel genes with enriched expression in human intermediate progenitors reveals a key role for CDKN3 in cortical development.

Overview

Authors: Pauline Antonie Ulmke1, Martin N. Ivanov2,3, Hoang Duy Nguyen1, Linh Pham1, Asisa Muchamedin1, Ayman Alzu’bi4, Lora V. Veleva3, Tsvetomir Kachovski5, Xiaoyi Mao1, Krzysztof P. Lubieniecki1, Emil Kovachev5, Gavin J. Clowry4, Anton B. Tonchev2,3, Huu Phuc Nguyen1, Tran Tuoc1
ORCID iDs: Lora V. Veleva, Tsvetomir Kachovski, Tran Tuoc
  1. Department of Human Genetics, Ruhr University Bochum, Bochum, Germany
  2. NutriLect Research Group, Research Institute, Medical University-Varna, Varna, Bulgaria
  3. Department of Anatomy and Cell Biology, Medical University-Varna, Varna, Bulgaria
  4. Newcastle University Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
  5. Specialized Hospital for Obstetrics and Gynecology “Prof. Dimitar Stamatov”–Varna, Medical University-Varna, Varna, Bulgaria
Institutions: Ruhr University Bochum (Germany); Medical University of Varna (Bulgaria); Newcastle University (United Kingdom)
Journal: Stem cell reports, volume 21, issue 8, article 103012
Dates: received 21 January 2025; accepted 11 June 2026; published online 9 July 2026; in print August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.stemcr.2026.103012 · PMID 42425091 · PMCID PMC13476879 · OpenAlex W7167849351
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: genetics / omics (modality), human (organism), mouse (organism), cellular / molecular (subfield)
Methods: Evoked potentials
Keywords: intermediate progenitor cells, transcriptome, cortical development, evolution, cortical malformation, transcription factors, signaling pathways, cell cycle regulation, CDKN3
MeSH: Gene Expression Regulation, Developmental*, Neocortex*, Neural Stem Cells*, Animals, Cell Proliferation, Gene Expression Profiling, Humans, Mice, Neurogenesis, Transcriptome (* major topic)
Topic: Neurogenesis and neuroplasticity mechanisms (Developmental Neuroscience, Neuroscience), according to OpenAlex
Funding: Deutsche Forschungsgemeinschaft (DFG) (F1008N-20, IF-027-22); RUB/FoRUM (GRK2862/1/492434978); NextGenerationEU via Bulgarian National Recovery and Resilience Plan (#BG-RRP-2.004-0009-C03)
Citations: not cited yet (Europe PMC); 97 references in the paper
Research resources: Mouse monoclonal BrdU (1:40) RRID:AB_10015219, Rat monoclonal EOMES/TBR2 (1:200) RRID:AB_11043546, RRID:AB_141373, RRID:AB_141611, RRID:AB_141658, RRID:AB_141778, RRID:AB_141874, RRID:AB_142924, RRID:AB_143165, RRID:AB_162543, Rabbit polyclonal mCherry/RFP (1:1000) RRID:AB_2209751, Mouse monoclonal TUBB3 (Tuj1) (1:200) RRID:AB_2210524, Mouse monoclonal HuC/HuD (HuCD) (1:20) RRID:AB_221448, RRID:AB_221605, Mouse monoclonal NeuN (1:200) RRID:AB_2298772, ImmPRESS HRP Anti-Mouse Ig Reagent RRID:AB_2336528, RRID:AB_2535764, Mouse monoclonal mCherry/RFP (1:1000) RRID:AB_2611063, ImmPRESS HRP Anti-Rabbit Ig Reagent RRID:AB_2631198, RRID:AB_2721040, Chicken polyclonal GFP (1:400) RRID:AB_300798, Rat monoclonal BrdU (1:100) RRID:AB_305426, Mouse monoclonal pHH3 (1:50) RRID:AB_331748, RRID:AB_3656306, Rabbit polyclonal human CDKN3 (1:200) RRID:AB_3665380, Rabbit polyclonal EOMES/TBR2 (1:200) RRID:AB_778267, Tbr2-2A-CreER mice, strain #:036301 RRID:IMSR_JAX:036301, DAVID RRID:SCR_001881, R RRID:SCR_001905, ImageJ RRID:SCR_003070, Galaxy web platform RRID:SCR_006281, featureCounts RRID:SCR_012919, Adobe Photoshop RRID:SCR_014199, FastQC RRID:SCR_014583, HISAT2 RRID:SCR_015530, DeSeq2 RRID:SCR_015687, Seurat RRID:SCR_016341, biomaRt RRID:SCR_019214, rtracklayer RRID:SCR_021325, Harmony RRID:SCR_022206, fasterq-dump tool (SRA Toolkit v3.0.3) RRID:SCR_024350

Abstract

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.

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

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none (its code is available on request), so it has no map.

Data

Datasets cited

Data and code availability

• 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.

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, issue, pages, dates, 15 authors, 9 keywords, 10 MeSH terms, 3 funders, 97 references, 41 RRIDs.

Cite

This paper

Ulmke, P. A., Ivanov, M. N., Nguyen, H. D., Pham, L., Muchamedin, A., Alzu’bi, A., Veleva, L. V., Kachovski, T., Mao, X., Lubieniecki, K. P., Kovachev, E., Clowry, G. J., Tonchev, A. B., Nguyen, H. P., & Tuoc, T. (2026). Identification of novel genes with enriched expression in human intermediate progenitors reveals a key role for CDKN3 in cortical development. Stem cell reports, 21(8), 103012. https://doi.org/10.1016/j.stemcr.2026.103012

BibTeX

@article{ulmke2026identification,
author = {Ulmke, Pauline Antonie and Ivanov, Martin N. and Nguyen, Hoang Duy and Pham, Linh and Muchamedin, Asisa and Alzu’bi, Ayman and Veleva, Lora V. and Kachovski, Tsvetomir and Mao, Xiaoyi and Lubieniecki, Krzysztof P. and Kovachev, Emil and Clowry, Gavin J. and Tonchev, Anton B. and Nguyen, Huu Phuc and Tuoc, Tran},
title = {{Identification of novel genes with enriched expression in human intermediate progenitors reveals a key role for CDKN3 in cortical development}},
journal = {Stem cell reports},
year = {2026},
month = jul,
volume = {21},
number = {8},
pages = {103012},
publisher = {Elsevier},
issn = {2213-6711},
doi = {10.1016/j.stemcr.2026.103012},
url = {https://doi.org/10.1016/j.stemcr.2026.103012},
pmid = {42425091},
pmcid = {PMC13476879}
}

RIS

TY - JOUR
AU - Ulmke, Pauline Antonie
AU - Ivanov, Martin N.
AU - Nguyen, Hoang Duy
AU - Pham, Linh
AU - Muchamedin, Asisa
AU - Alzu’bi, Ayman
AU - Veleva, Lora V.
AU - Kachovski, Tsvetomir
AU - Mao, Xiaoyi
AU - Lubieniecki, Krzysztof P.
AU - Kovachev, Emil
AU - Clowry, Gavin J.
AU - Tonchev, Anton B.
AU - Nguyen, Huu Phuc
AU - Tuoc, Tran
TI - Identification of novel genes with enriched expression in human intermediate progenitors reveals a key role for CDKN3 in cortical development
T2 - Stem cell reports
J2 - Stem Cell Reports
PY - 2026
DA - 2026/07/09
VL - 21
IS - 8
SP - 103012
SN - 2213-6711
PB - Elsevier
DO - 10.1016/j.stemcr.2026.103012
UR - https://doi.org/10.1016/j.stemcr.2026.103012
LA - en
ER -

CSL-JSON

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