ArticlebioRxiv : the preprint server for biology2025
Interspecies Organoids Reveal Human-Specific Molecular Features of Dopaminergic Neuron Development and Vulnerability.
Sara Nolbrant, Jenelle L Wallace, Jingwen W Ding, Tianjia Zhu, Jess L Sevetson, Janko Kajtez, Isabella A Baldacci, Emily K Corrigan, Kaylynn Hoglin, Reed McMullen and 11 more
Abstract readPreprint
In one paragraphArticle in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from itWhat it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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 registryThe 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.
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3 · Its place in the literatureWho cites it
0 citing papers in PubMed.
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4 · The recordCorrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
5 · Who and what moneyAuthors and funding
21 authors.
Sara NolbrantThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0003-2184-1741 Jenelle L WallaceThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-9565-2751 Jingwen W DingThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
Tianjia ZhuDepartment of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Jess L SevetsonDepartment of Molecular, Cellular, and Developmental Biology, University of California Santa Cruz, CA, United States of America.
Janko KajtezNovo Nordisk Foundation Center for Stem Cell Medicine (reNEW)), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0001-9997-2325 Isabella A BaldacciThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
Emily K CorriganThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-9072-7291 Kaylynn HoglinThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
Reed McMullenThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-1827-040X Megan S OstrowskiThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0001-9845-9319 Matthew T SchmitzThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-6177-8161 Arnar BreevoortThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-8929-9138 Dani SwopeThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
Fengxia WuDepartment of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Bryan J PavlovicThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-7751-5315 Sofie R SalamaDepartment of Molecular, Cellular, and Developmental Biology, University of California Santa Cruz, CA, United States of America.ORCID 0000-0001-6999-7193 Agnete KirkebyNovo Nordisk Foundation Center for Stem Cell Medicine (reNEW)), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0001-8203-6901 Hao HuangDepartment of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Nathan K SchaeferThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0001-5881-7329 Alex A PollenThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0003-3263-8634 Funding
Yerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesisP51OD011132 · OD · EMORY UNIVERSITY · PI Joon Sup Lee · 2012 to 2026
$167.0MNanoparticle Tracking Analyzer (NTA) for the Center for Live Cell GenomicsRM1HG011543 · NHGRI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI HAUSSLER, DAVID H, SALAMA, SOFIE REDA · 2021 to 2025
$12.0MPREDOCTORAL TRAINING IN DEVELOPMENTAL BIOLOGYT32HD007470 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Todd Nystul · 1994 to 2026
$7.7MHuman‐specific vulnerabilities and compensatory adaptations to age‐related stressors in selectively vulnerable midbrain dopaminergic neuronsR01AG087959 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KATHERINE S. POLLARD, ALEXANDER A POLLEN · 2024 to 2026
$4.2MIRACDA at UCSC and CSUMBK12GM139185 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI FORSBERG, CAMILLA, HINCK, LINDSAY E · 2020 to 2024
$4.1MDissecting the role of NOTCH2NL genes in human brain development and neurological disorders associated with chromosome 1q21.1 distal duplications and deletions.R01MH120295 · NIMH · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI SALAMA, SOFIE REDA · 2020 to 2024
$3.7MDiscovering human divergent activity-regulated elements using comparative, computational, and functional approachesR01MH134981 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KATHERINE S. POLLARD, ALEXANDER A POLLEN · 2023 to 2026
$3.3MEstablishing A Stem Cell Biology Platform for Decoding the Genetic Basis of Human Brain SpecializationsDP2MH122400 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI POLLEN, ALEXANDER A · 2019 to 2019
$2.4MIllumina NovaSeq 6000 Sequencing SystemS10OD028511 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHOW, ERIC D · 2020 to 2020
$583kNHGRI NIH HHS RM1 HG011543NIA NIH HHS R01 AG087959NICHD NIH HHS T32 HD007470NIGMS NIH HHS K12 GM139185NIH HHS P51 OD011132NIH HHS S10 OD028511NIMH NIH HHS DP2 MH122400NIMH NIH HHS R01 MH120295NIMH NIH HHS R01 MH134981
6 · The paper itselfAbstract
The disproportionate expansion of telencephalic structures during human evolution involved tradeoffs that imposed greater connectivity and metabolic demands on midbrain dopaminergic neurons. Despite the central role of dopaminergic neurons in human-enriched disorders, molecular specializations associated with human-specific features and vulnerabilities of the dopaminergic system remain unexplored. Here, we establish a phylogeny-in-a-dish approach to examine gene regulatory evolution by differentiating pools of human, chimpanzee, orangutan, and macaque pluripotent stem cells into ventral midbrain organoids capable of forming long-range projections, spontaneous activity, and dopamine release. We identify human-specific gene expression changes related to axonal transport of mitochondria and reactive oxygen species buffering and candidate
Indexed as
Brain evolutiondopaminergiciPSCsmidbrainorganoidsoxidative stressParkinson’s diseasesingle cell genomics
Identifiers
PMID39605599
PMCPMC11601475
What OpenQuestion holds
Textmetadata
LicenceCC BY-NC
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