Abstract
The adult human brain comprises more than a thousand distinct neuronal and glial cell types, a diversity that emerges during early brain development. To reveal the precise sequence of events during early brain development, we used single-cell RNA sequencing and spatial transcriptomics and uncovered cell states and trajectories in human brains at 5 to 14 postconceptional weeks (pcw). We identified 12 major classes that are organized as ~600 distinct cell states, which map to precise spatial anatomical domains at 5 pcw. We described detailed differentiation trajectories of the human forebrain and midbrain and found a large number of region-specific glioblasts that mature into distinct pre-astrocytes and pre–oligodendrocyte precursor cells. Our findings reveal the establishment of cell types during the first trimester of human brain development.
| Original language | English |
|---|---|
| Article number | eadf1226 |
| Journal | Science |
| Volume | 382 |
| Issue number | 6667 |
| DOIs | |
| State | Published - 13 Oct 2023 |
| Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2023 American Association for the Advancement of Science. All rights reserved.
Funding
We acknowledge the services of the Developmental Tissue Bank (Department of Neurobiology, Care Sciences and Society, Karolinska Institutet) for providing prenatal tissue and the National Genomics Infrastructure in Stockholm funded by Science for Life Laboratory, the Knut and Alice Wallenberg Foundation and the Swedish Research Council, and the SNIC/Uppsala Multidisciplinary Center for Advanced Computational Science for DNA sequencing and access to the UPPMAX computational infrastructure. We thank A. Zeisel (Technion, Israel), K. Siletti (Karolinska Institute), and all Linnarsson lab members for helpful discussions and P. Czarnewski (KTH Royal Institute of Technology) for assistance with data submissions. We thank S. Wyke for creating the summary figure. This publication is part of the Human Cell Atlas (https://humancellatlas.org/publications/). Funding: This work was supported by EMBO long-term fellowship ALTF 485-2019 (to M.D.-G.), grants from the Erling-Persson Foundation (HDCA to S.L., E.S., and J.L.), the Knut and Alice Wallenberg Foundation (2015.0041, 2018.0172 to S.L.; 2018.0220 to S.L., E.S., and J.L.; and 2018.0232 to E.A.), the Chan Zuckerberg Initiative and the Silicon Valley (NDCN 2018-191929 to E.A. and S.L.), the Swedish Foundation for Strategic Research (SB16-0065 to S.L. and E.A.), the Torsten Söderberg Foundation (to S.L.), the European Union (BRAINTIME to S.L. and ERC-ADG 884608 and H2020 874758 to E.A.), Vetenskapsrådet (2020-01426 to E.A.), the Karolinska Institutet (StratRegen SFO 2018 to E.A.), Hjärnfonden (FO2019-0068 to E.A.), and the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014 to R.A.B.). Any views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.
| Funders | Funder number |
|---|---|
| BRAINTIME | ERC-ADG 884608, H2020 874758 |
| Erling-Persson Foundation | |
| HDCA | 2018.0172, 2018.0220, 2015.0041, 2018.0232 |
| SNIC | |
| Silicon Valley | NDCN 2018-191929 |
| European Molecular Biology Organization | ALTF 485-2019 |
| Torsten Söderbergs Stiftelse | |
| Chan Zuckerberg Initiative | |
| National Institute for Health and Care Research | |
| European Commission | |
| Stiftelsen för Strategisk Forskning | SB16-0065 |
| Karolinska Institutet | |
| Knut och Alice Wallenbergs Stiftelse | |
| Vetenskapsrådet | 2020-01426, FO2019-0068 |
| Science for Life Laboratory | |
| Uppsala Multidisciplinary Center for Advanced Computational Science | |
| NIHR Cambridge Biomedical Research Centre | BRC-1215-20014 |