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Single-cell transcriptomics captures features of human midbrain development and dopamine neuron diversity in brain organoids

Author

Listed:
  • Alessandro Fiorenzano

    (Lund University)

  • Edoardo Sozzi

    (Lund University)

  • Marcella Birtele

    (Lund University)

  • Janko Kajtez

    (Lund University)

  • Jessica Giacomoni

    (Lund University)

  • Fredrik Nilsson

    (Lund University)

  • Andreas Bruzelius

    (Lund University)

  • Yogita Sharma

    (Lund University)

  • Yu Zhang

    (Lund University)

  • Bengt Mattsson

    (Lund University)

  • Jenny Emnéus

    (Technical University of Denmark)

  • Daniella Rylander Ottosson

    (Lund University)

  • Petter Storm

    (Lund University)

  • Malin Parmar

    (Lund University)

Abstract

Three-dimensional brain organoids have emerged as a valuable model system for studies of human brain development and pathology. Here we establish a midbrain organoid culture system to study the developmental trajectory from pluripotent stem cells to mature dopamine neurons. Using single cell RNA sequencing, we identify the presence of three molecularly distinct subtypes of human dopamine neurons with high similarity to those in developing and adult human midbrain. However, despite significant advancements in the field, the use of brain organoids can be limited by issues of reproducibility and incomplete maturation which was also observed in this study. We therefore designed bioengineered ventral midbrain organoids supported by recombinant spider-silk microfibers functionalized with full-length human laminin. We show that silk organoids reproduce key molecular aspects of dopamine neurogenesis and reduce inter-organoid variability in terms of cell type composition and dopamine neuron formation.

Suggested Citation

  • Alessandro Fiorenzano & Edoardo Sozzi & Marcella Birtele & Janko Kajtez & Jessica Giacomoni & Fredrik Nilsson & Andreas Bruzelius & Yogita Sharma & Yu Zhang & Bengt Mattsson & Jenny Emnéus & Daniella , 2021. "Single-cell transcriptomics captures features of human midbrain development and dopamine neuron diversity in brain organoids," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27464-5
    DOI: 10.1038/s41467-021-27464-5
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    References listed on IDEAS

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    1. Madeline A. Lancaster & Magdalena Renner & Carol-Anne Martin & Daniel Wenzel & Louise S. Bicknell & Matthew E. Hurles & Tessa Homfray & Josef M. Penninger & Andrew P. Jackson & Juergen A. Knoblich, 2013. "Cerebral organoids model human brain development and microcephaly," Nature, Nature, vol. 501(7467), pages 373-379, September.
    2. Giorgia Quadrato & Tuan Nguyen & Evan Z. Macosko & John L. Sherwood & Sung Min Yang & Daniel R. Berger & Natalie Maria & Jorg Scholvin & Melissa Goldman & Justin P. Kinney & Edward S. Boyden & Jeff W., 2017. "Cell diversity and network dynamics in photosensitive human brain organoids," Nature, Nature, vol. 545(7652), pages 48-53, May.
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    1. Pascale Baden & Maria Jose Perez & Hariam Raji & Federico Bertoli & Stefanie Kalb & María Illescas & Fokion Spanos & Claudio Giuliano & Alessandra Maria Calogero & Marvin Oldrati & Hannah Hebestreit &, 2023. "Glucocerebrosidase is imported into mitochondria and preserves complex I integrity and energy metabolism," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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