Skip to content
DraconiticResearch
Search Sources API
201,818 studies31 sourcesUpdated 31 min ago
Peer-reviewedCC BYNature Neuroscience

Single-cell multi-omic atlas and morphogen screening informs midbrain and hindbrain organoid engineering

  • Nadezhda V. Azbukina1
  • Zhisong He1
  • Hsiu‐Chuan Lin1
  • Małgorzata Santel1
  • Bijan Kashanian1
  • Ashley Maynard1
  • Tivadar Török1
  • Ryoko Okamoto1
  • Marina Tsvetomilova Nikolova1
  • Makiko Seimiya1
  • Sabina Kanton2
  • Valentin Brösamle1
3 more authors
  • René Holtackers1
  • J. Gray Camp3,4
  • Barbara Treutlein5
5 affiliations
  1. 1Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland
  2. 2Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
  3. 3Biozentrum, University of Basel, Basel, Switzerland. [email protected]
  4. 4Institute of Human Biology (IHB), Roche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland. [email protected]
  5. 5Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland. [email protected]
Open at sourceDOICite

Abstract

Patterning of the neural tube establishes midbrain and hindbrain structures that coordinate motor movement, process sensory input and integrate cognitive functions. Cellular impairment within these structures underlies diverse neurological disorders, and in vitro organoid models promise inroads to understanding development and modeling disease. Here, we use paired single-cell transcriptome and accessible chromatin sequencing to map cell composition and regulatory mechanisms in organoid models of midbrain and hindbrain. We find that existing midbrain organoid protocols generate ventral and dorsal cell types, covering regions including floor plate, dorsal and ventral midbrain and adjacent hindbrain regions. Gene regulatory network inference and transcription factor perturbation resolve mechanisms underlying neuronal differentiation. A single-cell multiplexed patterning screen identifies morphogen concentrations that expand existing organoid models, including conditions generating medulla glycinergic neurons and cerebellum glutamatergic subtypes. Together, the multi-omic atlas and morphogen screen reveal morphogen–regulon relationships guiding region-specific progenitor differentiation towards diverse neuron types of the posterior brain.

Related

  1. Reciprocal coupling between EMT and BMP morphogen signalling drives collective cell invasion
    Yuri Takahashi, Alexandra Neaverson, Lara Busby +4
    The EMBO JournalPeer-reviewedCC BY 4.0Full textMolecular biology & gene regulationPMC
  2. Dynamics of bicoid mRNA localisation and translation dictate morphogen gradient formation
    Thamarailingam Athilingam, Elise L Wilby, Pierre Bensidoun +7
    The EMBO JournalPeer-reviewedCC BY 4.0Full textMolecular biology & gene regulationPMCHAL
  3. Sharp cell type boundaries emerge from coordinated morphogen signaling
    Ruiqi Li, Yiqun Jiang, Sarah Platt +13
    Genes & DevelopmentPreprintCC BY-NC 4.0Full textMolecular biology & gene regulationPMC
  4. Spatiotemporally resolved single-nucleus transcriptomics reveals cellular and regional vulnerability in the midbrain in Parkinson’s disease
    Sooyeon Yoo, Kwanghoon Lee, Junseo Seo +7
    Signal Transduction and Targeted TherapyPeer-reviewedCC BY-NC-ND 4.0Full textMolecular biology & gene regulationPMCEurope PMC
  5. Modulation of WNT and FGF18 enhances yield and subtype identity of hPSC-derived midbrain dopamine neurons
    T Kim, Jinghua Piao, Vittoria Dickinson Bocchi +19
    Journal of Clinical InvestigationPeer-reviewedCC BY10 citedMolecular biology & gene regulationOpenAlex

Cite

BibTeXRIS
BibTeX
@article{azbukina2026singlecell,
  title = {{Single-cell multi-omic atlas and morphogen screening informs midbrain and hindbrain organoid engineering}},
  author = {Nadezhda V. Azbukina and Zhisong He and Hsiu‐Chuan Lin and Małgorzata Santel and Bijan Kashanian and Ashley Maynard and Tivadar Török and Ryoko Okamoto and Marina Tsvetomilova Nikolova and Makiko Seimiya and Sabina Kanton and Valentin Brösamle and René Holtackers and J. Gray Camp and Barbara Treutlein},
  journal = {Nature Neuroscience},
  year = {2026},
  month = jun,
  doi = {10.1038/s41593-026-02316-x},
  url = {https://doi.org/10.1038/s41593-026-02316-x},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Single-cell multi-omic atlas and morphogen screening informs midbrain and hindbrain organoid engineering
AU  - Nadezhda V. Azbukina
AU  - Zhisong He
AU  - Hsiu‐Chuan Lin
AU  - Małgorzata Santel
AU  - Bijan Kashanian
AU  - Ashley Maynard
AU  - Tivadar Török
AU  - Ryoko Okamoto
AU  - Marina Tsvetomilova Nikolova
AU  - Makiko Seimiya
AU  - Sabina Kanton
AU  - Valentin Brösamle
AU  - René Holtackers
AU  - J. Gray Camp
AU  - Barbara Treutlein
PY  - 2026
DA  - 2026/06/03
JO  - Nature Neuroscience
DO  - 10.1038/s41593-026-02316-x
UR  - https://doi.org/10.1038/s41593-026-02316-x
AB  - Patterning of the neural tube establishes midbrain and hindbrain structures that coordinate motor movement, process sensory input and integrate cognitive functions. Cellular impairment within these structures underlies diverse neurological disorders, and in vitro organoid models promise inroads to understanding development and modeling disease. Here, we use paired single-cell transcriptome and accessible chromatin sequencing to map cell composition and regulatory mechanisms in organoid models of midbrain and hindbrain. We find that existing midbrain organoid protocols generate ventral and dorsal cell types, covering regions including floor plate, dorsal and ventral midbrain and adjacent hindbrain regions. Gene regulatory network inference and transcription factor perturbation resolve mechanisms underlying neuronal differentiation. A single-cell multiplexed patterning screen identifies morphogen concentrations that expand existing organoid models, including conditions generating medulla glycinergic neurons and cerebellum glutamatergic subtypes. Together, the multi-omic atlas and morphogen screen reveal morphogen–regulon relationships guiding region-specific progenitor differentiation towards diverse neuron types of the posterior brain.
SN  - 1097-6256
SN  - 1546-1726
ER  -