| Field |
Value |
| Identifier |
nemo:dat-bmx7s1t |
| Dataset Name |
A concerted neuron–astrocyte program declines in ageing and schizophrenia |
| Version |
NA |
| Release Date |
NA |
| DOI |
NA |
| Source Data URL |
This is a restricted access dataset. Instructions for requesting access are available at https://nemoarchive.org/resources/accessing-controlled-access-data#broad-dac-approval-process |
| Dataset Collection URL |
https://data.nemoarchive.org/publication_release/Broad_SZ_sn_10xv3_2024-bag-2024-12-03.tgz |
| Description |
Human brains vary in health and in illness. To better understand human neurobiological variation, we used single-nucleus RNA-seq to analyze 1.2 million nuclei from the prefrontal cortex of 191 persons, including 94 affected by schizophrenia. Cortical neurons and astrocytes exhibited a striking relationship, even among neurotypical control individuals: in brain samples in which neurons invested more transcription in synaptic components, astrocytes invested more transcription in genes with synaptic functions and in genes for synthesizing cholesterol, an astrocyte-supplied component of synaptic membranes. We call this relationship the Synaptic Neuron-and-Astrocyte Program (SNAP). SNAP expression was reduced in brain tissue from donors with schizophrenia, in astrocytes and in cortical neurons of all types. Previously-identified genetic risk factors for schizophrenia were concentrated in the genes SNAP regulated in astrocytes, as well as the genes SNAP regulated in neurons. Further evidence for the significance of neurons and astrocytes in schizophrenia was found among 11,356 cell-type-specific expression QTLs we mapped using these data. SNAP, and perhaps other such transcellular programs, may be important aspects of normal biological variation and pathophysiology. |
| Keywords |
human, cortex, dlPFC |
| Total Files in Collection |
24139 |
| Total Size in Collection (in GB) |
29529.7 |
| Authors |
Emi Ling, James Nemesh, Melissa Goldman, Nolan Kamitaki, Nora Reed, Robert E. Handsaker, Giulio Genovese, Jonathan S. Vogelgsang, Sherif Gerges, Seva Kashin, Sulagna Ghosh, John M. Esposito, Kiely French, Daniel Meyer, Alyssa Lutservitz, Christopher D. Mullally, Alec Wysoker, Liv Spina, Anna Neumann, Marina Hogan, Kiku Ichihara, Sabina Berretta, Steven A. McCarroll |
| Organization |
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Program in Neuroscience, Harvard Medical School, Boston, MA 02215, USA; McLean Hospital, Belmont, MA 02478, USA; Department of Psychiatry, Harvard Medical School, Boston, MA 02215, USA |
| Contact Person |
Emi Ling |
| Contact E-Mail |
eling@broadinstitute.org |
| External Identifier |
https://doi.org/10.1038/s41586-024-07109-5 |
| Grant Name |
Broad Institute's Stanley Center for Psychiatric Research, the National Institute of Mental Health (grant U01MH115727), and the National Institutes of Health (T32 HG002295) |
| Consortium |
NA |
| Data Repository |
NeMO |
| Data Repository RRID |
RRID:SCR_016152 |
| Data License |
NA |
| Data Access |
NA |
| Community Standards |
NA |
| Study Organism |
human |
| Protocol ID |
dx.doi.org/10.17504/protocols.io.4r3l22e3xl1y/v1 |
