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Landscape of human spinal cord cell type diversity at midgestation

View ORCID ProfileJimena Andersen, View ORCID ProfileNicholas Thom, View ORCID ProfileJennifer L. Shadrach, View ORCID ProfileXiaoyu Chen, View ORCID ProfileNeal D. Amin, View ORCID ProfileSe-Jin Yoon, View ORCID ProfileWilliam J. Greenleaf, View ORCID ProfileFabian Müller, View ORCID ProfileAnca M. Pașca, View ORCID ProfileJulia A. Kaltschmidt, View ORCID ProfileSergiu Pașca
doi: https://doi.org/10.1101/2021.12.29.473693
Jimena Andersen
1Department of Psychiatry and Behavioral Sciences, Stanford University, USA
2Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute, USA
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  • ORCID record for Jimena Andersen
Nicholas Thom
1Department of Psychiatry and Behavioral Sciences, Stanford University, USA
2Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute, USA
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Jennifer L. Shadrach
3Department of Neurosurgery, Stanford University, USA
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Xiaoyu Chen
1Department of Psychiatry and Behavioral Sciences, Stanford University, USA
2Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute, USA
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Neal D. Amin
1Department of Psychiatry and Behavioral Sciences, Stanford University, USA
2Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute, USA
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Se-Jin Yoon
1Department of Psychiatry and Behavioral Sciences, Stanford University, USA
2Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute, USA
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William J. Greenleaf
4Department of Genetics, Stanford University, USA
5Department of Applied Physics, Stanford University, USA
6Chan–Zuckerberg Biohub, San Francisco, USA
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Fabian Müller
4Department of Genetics, Stanford University, USA
7Center for Bioinformatics, Saarland University, Germany
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  • ORCID record for Fabian Müller
Anca M. Pașca
8Department of Pediatrics, Division of Neonatology, Stanford University, USA
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  • ORCID record for Anca M. Pașca
Julia A. Kaltschmidt
3Department of Neurosurgery, Stanford University, USA
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Sergiu Pașca
1Department of Psychiatry and Behavioral Sciences, Stanford University, USA
2Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute, USA
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  • For correspondence: spasca@stanford.edu
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Abstract

Understanding spinal cord generation and assembly is essential to elucidate how motor behavior is controlled and how disorders arise. The cellular landscape of the human spinal cord remains, however, insufficiently explored. Here, we profiled the midgestation human spinal cord with single cell-resolution and discovered, even at this fetal stage, remarkable heterogeneity across and within cell types. Glia displayed diversity related to positional identity along the dorso-ventral and rostro-caudal axes, while astrocytes with specialized transcriptional programs mapped onto distinct histological domains. We discovered a surprisingly early diversification of alpha (α) and gamma (γ) motor neurons that control and modulate contraction of muscle fibers, which was suggestive of accelerated developmental timing in human spinal cord compared to rodents. Together with mapping of disease-related genes, this transcriptional profile of the developing human spinal cord opens new avenues for interrogating the cellular basis of motor control and related disorders in humans.

Competing Interest Statement

W.J.G. was a consultant for 10x Genomics.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 29, 2021.
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Landscape of human spinal cord cell type diversity at midgestation
Jimena Andersen, Nicholas Thom, Jennifer L. Shadrach, Xiaoyu Chen, Neal D. Amin, Se-Jin Yoon, William J. Greenleaf, Fabian Müller, Anca M. Pașca, Julia A. Kaltschmidt, Sergiu Pașca
bioRxiv 2021.12.29.473693; doi: https://doi.org/10.1101/2021.12.29.473693
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Landscape of human spinal cord cell type diversity at midgestation
Jimena Andersen, Nicholas Thom, Jennifer L. Shadrach, Xiaoyu Chen, Neal D. Amin, Se-Jin Yoon, William J. Greenleaf, Fabian Müller, Anca M. Pașca, Julia A. Kaltschmidt, Sergiu Pașca
bioRxiv 2021.12.29.473693; doi: https://doi.org/10.1101/2021.12.29.473693

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