Evidence map›Paper›PMID 42785308›Full record

ArticleStem cell reports2026

HOPX regulates the development and lineage progression of human stem cell-derived outer radial glia-like cells.

Xiao-Xue Dong, Wendy W Y Choi, Mai Ahmed, Haruka Nishimura, Ai Tian, David Millar, Afrin Bhattacharya, Aditi Aggarwal, Liona Vu, Octavia Yifang Weng and 9 more

Abstract read
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Article in Stem cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Xiao-Xue DongDepartment of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No.86, Wujin Road, Shanghai 200080, China; Program in Developmental, Stem Cell, and Cancer Biology, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada; The Children's Hospital, National Clinical Research Center for Child Health, School of Medicine, Zhejiang University, Hangzhou 310052, China; The Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310029, China.
Wendy W Y ChoiProgram in Developmental, Stem Cell, and Cancer Biology, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Program in Genetics and Genome Biology, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada.
Mai AhmedProgram in Developmental, Stem Cell, and Cancer Biology, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada.
Haruka NishimuraProgram in Developmental, Stem Cell, and Cancer Biology, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Ai TianProgram in Neurosciences and Mental Health, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada.
David MillarDepartment of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Program in Neurosciences and Mental Health, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada.
Afrin BhattacharyaProgram in Developmental, Stem Cell, and Cancer Biology, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Aditi AggarwalProgram in Developmental, Stem Cell, and Cancer Biology, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Liona VuProgram in Developmental, Stem Cell, and Cancer Biology, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Octavia Yifang WengProgram in Developmental, Stem Cell, and Cancer Biology, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Program in Neurosciences and Mental Health, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Roseanne NguyenDepartment of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Program in Neurosciences and Mental Health, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada.
Pragnya ChakrabortyProgram in Developmental, Stem Cell, and Cancer Biology, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada.
Lu-Yang WangProgram in Neurosciences and Mental Health, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Michael D WilsonDepartment of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Program in Genetics and Genome Biology, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada.
Qiang ShuThe Children's Hospital, National Clinical Research Center for Child Health, School of Medicine, Zhejiang University, Hangzhou 310052, China; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Xuekun LiThe Children's Hospital, National Clinical Research Center for Child Health, School of Medicine, Zhejiang University, Hangzhou 310052, China; The Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310029, China.
Yun-Cheng WuDepartment of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No.86, Wujin Road, Shanghai 200080, China. Electronic address: yunchw@medmail.com.cn.
Julien MuffatDepartment of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Program in Neurosciences and Mental Health, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada. Electronic address: julien.muffat@sickkids.ca.
Yun LiProgram in Developmental, Stem Cell, and Cancer Biology, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada. Electronic address: yun.li@sickkids.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Outer radial glia (oRG) are abundant in the human fetal cortex but rare in rodents, yet their molecular regulation remains poorly understood. Although the homeodomain-only protein X (HOPX) is a well-established oRG marker, its functional role in human cortical development remains undefined. Using CRISPR-Cas9 gene editing in human pluripotent stem cells, we show that HOPX loss impairs the expansion and lineage progression of oRG-like cells in two-dimensional neural cultures and three-dimensional cortical organoids. HOPX knockout precursors exhibit reduced proliferation, diminished neurogenesis, and premature differentiation toward astrocytic and oligodendrocytic lineages. HOPX-deficient organoids display reduced outer subventricular zone size, decreased neuronal output, and early gliogenesis. Mechanistically, HOPX loss impairs PI3K-mTOR signaling. Transcriptomic analysis identifies HOPX-regulated programs governing gliogenic competence, mTOR, and Wnt signaling. Together, these findings identify HOPX as an important regulator of oRG-like cell maintenance and the neurogenic-gliogenic balance, providing insight into the molecular programs governing human neural progenitor expansion.

Indexed as

Cell LineageEpendymoglial CellsHomeodomain ProteinsNeural Stem CellsCell DifferentiationCell ProliferationCRISPR-Cas SystemsHumansNeurogenesisNeuronsOrganoidsPhosphatidylinositol 3-KinasesSignal TransductionTOR Serine-Threonine KinasesHomeodomain ProteinsPhosphatidylinositol 3-KinasesTOR Serine-Threonine Kinasesbrain organoidsCRISPRHOPXneural developmentneural stem cellsneuronsouter radial glia

Identifiers

PMID42785308
PMCPMC13681406

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.