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Human-biased <i>MEIS1</i> expression by a promoter noncoding RNA regulates neural stem cell proliferation.

Overview

Authors: Hayato Uchida1, Tomonori Kameda1,2, Shota Zenno1, Hideyuki Nakashima2, Yuki Minato1, Yuina Aritsuka1, Sota Nishida1, Boyang An1, Mizuki Honda1, Fumihiro Morishita1, Kinichi Nakashima2, Takuya Imamura1
ORCID iDs: Mizuki Honda, Kinichi Nakashima, Takuya Imamura
  1. Program of Biomedical Science, Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima, Japan
  2. Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Institutions: Hiroshima University (Japan); Kyushu University (Japan)
Journal: Life science alliance, volume 9, issue 12, article e202603708
Dates: received 21 March 2026; accepted 18 September 2026; published online 30 September 2026; in print December 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.26508/lsa.202603708 · PMID 42816420 · PMCID PMC13627767 · OpenAlex W7215088919
Open access: gold, a free copy (OpenAlex)
Status: data only (how the code is found and verified)
Categories: human (organism), mouse (organism)
Methods: Evoked potentials
MeSH: Myeloid Ecotropic Viral Integration Site 1 Protein*, Neural Stem Cells*, RNA, Untranslated*, Animals, Cell Differentiation, Cell Proliferation, Cholesterol, Humans, Mice, Promoter Regions, Genetic (* major topic)
Topic: Genetic and Kidney Cyst Diseases (Genetics, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Uehara Memorial Foundation; Mitsubishi Foundation; Daiichi Sankyo Foundation of Life Science; Kobayashi Foundation for Cancer Research; NOVARTIS Foundation (Japan) for the Promotion of Science; Japan Society for the Promotion of Science (22H02531, 19H03138, 24K21918); Natural Science Center for Basic Research and Development, Hiroshima University (NBARD-00122)
Citations: not cited yet (Europe PMC); 63 references in the paper

Abstract

Whereas primate-specific genes are known to drive human evolution, conserved genes also play critical roles in defining species-specific traits. This study identifies MEIS1 as a key conserved gene with significantly higher expression in human radial glia compared with those in mice. Our functional analysis revealed that MEIS1 knockdown (KD) in human cerebral organoids leads to premature neural differentiation. Conversely, MEIS1 overexpression in the mouse brain significantly increases the abundance of neural progenitor cells (NPCs). By investigating a noncoding RNA (ncRNA) partner derived from the MEIS1 promoter, we demonstrated that its KD triggers MEIS1 down-regulation, markedly reducing NPC proliferative capacity. RNA-sequencing further indicated that MEIS1 regulates genes involved in cholesterol biogenesis. Specifically, forced expression of DHCR7, a MEIS1-target gene, rescued both the proliferative deficits and the reduction in primary cilia length induced by MEIS1 KD. These findings suggest that ncRNA-mediated regulatory mechanism for the conserved MEIS1 coordinates primary cilia morphology and cholesterol metabolism. This coordination is essential for maintaining long-term NPC properties, ultimately contributing to the evolutionary expansion of the human cerebral cortex.

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

Code

The paper links to its data and to no code of its authors: see the Data section.

Tracing map

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Data

Datasets cited

Data Availability

The raw sequencing data have been deposited in Gene Expression Omnibus under accession number GSE322827 (https://ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE322827) (RNA-seq) and GSE323332 (https://ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE323332) (ChIP-seq).

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, 6 October 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 12 authors, 10 MeSH terms, 7 funders, 63 references.

Cite

This paper

Uchida, H., Kameda, T., Zenno, S., Nakashima, H., Minato, Y., Aritsuka, Y., Nishida, S., An, B., Honda, M., Morishita, F., Nakashima, K., & Imamura, T. (2026). Human-biased <i>MEIS1</i> expression by a promoter noncoding RNA regulates neural stem cell proliferation. Life science alliance, 9(12), e202603708. https://doi.org/10.26508/lsa.202603708

BibTeX

@article{uchida2026human,
author = {Uchida, Hayato and Kameda, Tomonori and Zenno, Shota and Nakashima, Hideyuki and Minato, Yuki and Aritsuka, Yuina and Nishida, Sota and An, Boyang and Honda, Mizuki and Morishita, Fumihiro and Nakashima, Kinichi and Imamura, Takuya},
title = {{Human-biased \<i\>MEIS1\</i\> expression by a promoter noncoding RNA regulates neural stem cell proliferation}},
journal = {Life science alliance},
year = {2026},
month = sep,
volume = {9},
number = {12},
pages = {e202603708},
publisher = {Life Science Alliance LLC},
issn = {2575-1077},
doi = {10.26508/lsa.202603708},
url = {https://doi.org/10.26508/lsa.202603708},
pmid = {42816420},
pmcid = {PMC13627767}
}

RIS

TY - JOUR
AU - Uchida, Hayato
AU - Kameda, Tomonori
AU - Zenno, Shota
AU - Nakashima, Hideyuki
AU - Minato, Yuki
AU - Aritsuka, Yuina
AU - Nishida, Sota
AU - An, Boyang
AU - Honda, Mizuki
AU - Morishita, Fumihiro
AU - Nakashima, Kinichi
AU - Imamura, Takuya
TI - Human-biased <i>MEIS1</i> expression by a promoter noncoding RNA regulates neural stem cell proliferation
T2 - Life science alliance
J2 - Life Sci Alliance
PY - 2026
DA - 2026/09/30
VL - 9
IS - 12
SP - e202603708
SN - 2575-1077
PB - Life Science Alliance LLC
DO - 10.26508/lsa.202603708
UR - https://doi.org/10.26508/lsa.202603708
LA - en
ER -

CSL-JSON

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