IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-43471-0.html
   My bibliography  Save this article

Enhanced production of mesencephalic dopaminergic neurons from lineage-restricted human undifferentiated stem cells

Author

Listed:
  • Muyesier Maimaitili

    (Aarhus University
    Aarhus University)

  • Muwan Chen

    (Aarhus University
    Aarhus University)

  • Fabia Febbraro

    (Aarhus University
    Aarhus University Hospital)

  • Ekin Ucuncu

    (Aarhus University
    Aarhus University)

  • Rachel Kelly

    (Aarhus University
    Aarhus University)

  • Jonathan Christos Niclis

    (Cell Therapy Discovery, Cell Therapy R&D, Novo Nordisk)

  • Josefine Rågård Christiansen

    (Cell Therapy Discovery, Cell Therapy R&D, Novo Nordisk)

  • Noëmie Mermet-Joret

    (Aarhus University
    Aarhus University
    Aarhus University)

  • Dragos Niculescu

    (Aarhus University
    Aarhus University
    Aarhus University)

  • Johanne Lauritsen

    (Aarhus University
    Aarhus University)

  • Angelo Iannielli

    (Stem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute
    CNR Institute of Neuroscience)

  • Ida H. Klæstrup

    (Aarhus University
    Aarhus University)

  • Uffe Birk Jensen

    (Aarhus University
    Aarhus University Hospital)

  • Per Qvist

    (Aarhus University
    Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH
    Aarhus University
    Aarhus University)

  • Sadegh Nabavi

    (Aarhus University
    Aarhus University
    Aarhus University)

  • Vania Broccoli

    (Stem Cell and Neurogenesis Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute
    CNR Institute of Neuroscience)

  • Anders Nykjær

    (Aarhus University
    Aarhus University
    Aarhus University)

  • Marina Romero-Ramos

    (Aarhus University
    Aarhus University)

  • Mark Denham

    (Aarhus University
    Aarhus University)

Abstract

Current differentiation protocols for generating mesencephalic dopaminergic (mesDA) neurons from human pluripotent stem cells result in grafts containing only a small proportion of mesDA neurons when transplanted in vivo. In this study, we develop lineage-restricted undifferentiated stem cells (LR-USCs) from pluripotent stem cells, which enhances their potential for differentiating into caudal midbrain floor plate progenitors and mesDA neurons. Using a ventral midbrain protocol, 69% of LR-USCs become bona fide caudal midbrain floor plate progenitors, compared to only 25% of human embryonic stem cells (hESCs). Importantly, LR-USCs generate significantly more mesDA neurons under midbrain and hindbrain conditions in vitro and in vivo. We demonstrate that midbrain-patterned LR-USC progenitors transplanted into 6-hydroxydopamine-lesioned rats restore function in a clinically relevant non-pharmacological behavioral test, whereas midbrain-patterned hESC-derived progenitors do not. This strategy demonstrates how lineage restriction can prevent the development of undesirable lineages and enhance the conditions necessary for mesDA neuron generation.

Suggested Citation

  • Muyesier Maimaitili & Muwan Chen & Fabia Febbraro & Ekin Ucuncu & Rachel Kelly & Jonathan Christos Niclis & Josefine Rågård Christiansen & Noëmie Mermet-Joret & Dragos Niculescu & Johanne Lauritsen & , 2023. "Enhanced production of mesencephalic dopaminergic neurons from lineage-restricted human undifferentiated stem cells," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43471-0
    DOI: 10.1038/s41467-023-43471-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43471-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-43471-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Trygve E. Bakken & Nikolas L. Jorstad & Qiwen Hu & Blue B. Lake & Wei Tian & Brian E. Kalmbach & Megan Crow & Rebecca D. Hodge & Fenna M. Krienen & Staci A. Sorensen & Jeroen Eggermont & Zizhen Yao & , 2021. "Comparative cellular analysis of motor cortex in human, marmoset and mouse," Nature, Nature, vol. 598(7879), pages 111-119, October.
    2. Vania Broccoli & Edoardo Boncinelli & Wolfgang Wurst, 1999. "The caudal limit of Otx2 expression positions the isthmic organizer," Nature, Nature, vol. 401(6749), pages 164-168, September.
    3. Zhanna Alekseenko & José M. Dias & Andrew F. Adler & Mariya Kozhevnikova & Josina Anna Lunteren & Sara Nolbrant & Ashwini Jeggari & Svitlana Vasylovska & Takashi Yoshitake & Jan Kehr & Marie Carlén & , 2022. "Robust derivation of transplantable dopamine neurons from human pluripotent stem cells by timed retinoic acid delivery," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Sungyong Um & Bin Zhang & Sunil Wattal & Youngjin Yoo, 2023. "Software Components and Product Variety in a Platform Ecosystem: A Dynamic Network Analysis of WordPress," Information Systems Research, INFORMS, vol. 34(4), pages 1339-1374, December.
    2. Nelson Johansen & Hongru Hu & Gerald Quon, 2023. "Projecting RNA measurements onto single cell atlases to extract cell type-specific expression profiles using scProjection," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Tingting Bo & Jie Li & Ganlu Hu & Ge Zhang & Wei Wang & Qian Lv & Shaoling Zhao & Junjie Ma & Meng Qin & Xiaohui Yao & Meiyun Wang & Guang-Zhong Wang & Zheng Wang, 2023. "Brain-wide and cell-specific transcriptomic insights into MRI-derived cortical morphology in macaque monkeys," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Yuyao Song & Zhichao Miao & Alvis Brazma & Irene Papatheodorou, 2023. "Benchmarking strategies for cross-species integration of single-cell RNA sequencing data," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Jia-Ru Wei & Zhao-Zhe Hao & Chuan Xu & Mengyao Huang & Lei Tang & Nana Xu & Ruifeng Liu & Yuhui Shen & Sarah A. Teichmann & Zhichao Miao & Sheng Liu, 2022. "Identification of visual cortex cell types and species differences using single-cell RNA sequencing," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    6. Daniel J. Lodge & Hannah B. Elam & Angela M. Boley & Jennifer J. Donegan, 2023. "Discrete hippocampal projections are differentially regulated by parvalbumin and somatostatin interneurons," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    7. Ian Covert & Rohan Gala & Tim Wang & Karel Svoboda & Uygar Sümbül & Su-In Lee, 2023. "Predictive and robust gene selection for spatial transcriptomics," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    8. Thomas M. Goralski & Lindsay Meyerdirk & Libby Breton & Laura Brasseur & Kevin Kurgat & Daniella DeWeerd & Lisa Turner & Katelyn Becker & Marie Adams & Daniel J. Newhouse & Michael X. Henderson, 2024. "Spatial transcriptomics reveals molecular dysfunction associated with cortical Lewy pathology," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    9. Malosree Maitra & Haruka Mitsuhashi & Reza Rahimian & Anjali Chawla & Jennie Yang & Laura M. Fiori & Maria Antonietta Davoli & Kelly Perlman & Zahia Aouabed & Deborah C. Mash & Matthew Suderman & Nagu, 2023. "Cell type specific transcriptomic differences in depression show similar patterns between males and females but implicate distinct cell types and genes," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    10. Junhao Li & Manoj K. Jaiswal & Jo-Fan Chien & Alexey Kozlenkov & Jinyoung Jung & Ping Zhou & Mahammad Gardashli & Luc J. Pregent & Erica Engelberg-Cook & Dennis W. Dickson & Veronique V. Belzil & Eran, 2023. "Divergent single cell transcriptome and epigenome alterations in ALS and FTD patients with C9orf72 mutation," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    11. Jing-Ping Lin & Hannah M. Kelly & Yeajin Song & Riki Kawaguchi & Daniel H. Geschwind & Steven Jacobson & Daniel S. Reich, 2022. "Transcriptomic architecture of nuclei in the marmoset CNS," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    12. Seppe Goovaerts & Hanne Hoskens & Ryan J. Eller & Noah Herrick & Anthony M. Musolf & Cristina M. Justice & Meng Yuan & Sahin Naqvi & Myoung Keun Lee & Dirk Vandermeulen & Heather L. Szabo-Rogers & Pau, 2023. "Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    13. Michael Wainberg & Natalie J. Forde & Salim Mansour & Isabel Kerrebijn & Sarah E. Medland & Colin Hawco & Shreejoy J. Tripathy, 2024. "Genetic architecture of the structural connectome," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    14. Ying Lei & Mengnan Cheng & Zihao Li & Zhenkun Zhuang & Liang Wu & Yunong sun & Lei Han & Zhihao Huang & Yuzhou Wang & Zifei Wang & Liqin Xu & Yue Yuan & Shang Liu & Taotao Pan & Jiarui Xie & Chuanyu L, 2022. "Spatially resolved gene regulatory and disease-related vulnerability map of the adult Macaque cortex," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    15. Lucia Prado & Myriam Jaraíz-Rodríguez & Mauro Agro & Marcos Zamora-Dorta & Natalia Azpiazu & Manuel Calleja & Mario Lopez-Manzaneda & Jaime Juan-Sanz & Alba Fernández-Rodrigo & José A. Esteban & Mònic, 2024. "Compensatory activity of the PC-ME1 metabolic axis underlies differential sensitivity to mitochondrial complex I inhibition," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    16. Leonardo D. Garma & Lisbeth Harder & Juan M. Barba-Reyes & Sergio Marco Salas & Mónica Díez-Salguero & Mats Nilsson & Alberto Serrano-Pozo & Bradley T. Hyman & Ana B. Muñoz-Manchado, 2024. "Interneuron diversity in the human dorsal striatum," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    17. Yoav Ben-Simon & Karola Kaefer & Philipp Velicky & Jozsef Csicsvari & Johann G. Danzl & Peter Jonas, 2022. "A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    18. Kian Kalhor & Chien-Ju Chen & Ho Suk Lee & Matthew Cai & Mahsa Nafisi & Richard Que & Carter R. Palmer & Yixu Yuan & Yida Zhang & Xuwen Li & Jinghui Song & Amanda Knoten & Blue B. Lake & Joseph P. Gau, 2024. "Mapping human tissues with highly multiplexed RNA in situ hybridization," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    19. Fang Guo & Jun Fan & Jin-Ming Liu & Peng-Li Kong & Jing Ren & Jia-Wen Mo & Cheng-Lin Lu & Qiu-Ling Zhong & Liang-Yu Chen & Hao-Tian Jiang & Canyuan Zhang & You-Lu Wen & Ting-Ting Gu & Shu-Ji Li & Ying, 2024. "Astrocytic ALKBH5 in stress response contributes to depressive-like behaviors in mice," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    20. Yuqiu Zhou & Wei He & Weizhen Hou & Ying Zhu, 2024. "Pianno: a probabilistic framework automating semantic annotation for spatial transcriptomics," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43471-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.