Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in an Alzheimer disease model
Creators
- 1. Broad Institute of MIT and Harvard, Cambridge, MA, USA. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
- 2. Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- 3. Department of Neuroscience, Genentech, Inc., 1 DNA Way, South San Francisco, CA, USA.
- 4. Broad Institute of MIT and Harvard, Cambridge, MA, USA. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- 5. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
- 6. John A. Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA, USA.
Description
Amyloid-β plaques and neurofibrillary tau tangles are the neuropathologic hallmarks of Alzheimer’s disease (AD), but the spatiotemporal cellular responses and molecular mechanisms underlying AD pathophysiology remain poorly understood. Here we introduce STARmap PLUS to simultaneously map single-cell transcriptional states and disease marker proteins in brain tissues of AD mouse models at a voxel size of 95 95 350 nm. This high-resolution spatial transcriptomics map revealed a core-shell structure where disease-associated microglia (DAM) closely contact amyloid-β plaques, whereas disease-associated astrocyte-like cells (DAA-like) and oligodendrocyte precursor cells (OPC) are enriched in the outer shells surrounding the plaque-DAM complex. Hyperphosphorylated tau emerged mainly in excitatory neurons in the CA1 region accompanied by infiltration of oligodendrocyte subtypes into the axon bundles of hippocampal alveus. The integrative STARmap PLUS method bridges single-cell gene expression profiles with tissue histopathology at subcellular resolution, providing an unprecedented roadmap to pinpoint the molecular and cellular mechanisms of AD pathology and neurodegeneration.
Files
2022-01-11-mAD-64-genes-processed-images.zip
Files
(16.5 GB)
Name | Size | Download all |
---|---|---|
md5:26037d32fa89bae9221fd8f279c4d2da
|
589.2 MB | Preview Download |
md5:a7f5a84973bf7bfd58ebb1ea03a7bb3c
|
48.5 MB | Preview Download |
md5:147187eb35bb04c8218af243d5220b4a
|
14.2 GB | Preview Download |
md5:b94eb7e2681006c1ee28f187a0c63a12
|
428.7 kB | Preview Download |
md5:b879e43746e7fe4ae08e6276d22605f3
|
388.2 kB | Preview Download |
md5:a73615bf9b398bf3bc26dc84a7d2f1eb
|
870.1 MB | Preview Download |
md5:817fcf50ee96e727c1288d8da4bfb17c
|
16.1 MB | Preview Download |
md5:f91b3b1203cb04a1a965c846f5f19314
|
798.9 MB | Preview Download |
md5:3707e753b33219422a8920451bb3a407
|
17.9 MB | Preview Download |
md5:3acb9a72c317a76f78725a4ee4085d26
|
6.8 MB | Preview Download |
md5:f4692dc71346c4ce035b95ba86304766
|
234.9 kB | Preview Download |
md5:596d6075b1e1e29d069aa46de6a2c32a
|
213.6 kB | Preview Download |
md5:0f15f2fd49fcf36a5b7604c6b344ca6c
|
792.6 kB | Preview Download |
md5:de1b533148b9fc66544821f86a691a13
|
725.2 kB | Preview Download |
md5:6a0eee3738b8a39d26e851d3ad74aad2
|
32.3 kB | Preview Download |
md5:3413757e5ed3ef5bc23bd1f240cb206b
|
22.9 kB | Preview Download |
md5:e917972e951b4ff36e0c69308ca6b193
|
14.9 kB | Preview Download |
md5:e2af28b2b728e4921516fd49b70bf5fe
|
16.8 kB | Preview Download |
md5:e682cb0d156270cd2c487a03d4781cb6
|
543.9 kB | Preview Download |
md5:86271b841d123898c47d2ad107603c68
|
634.1 kB | Preview Download |
md5:cfc7385c55fe0769d0f2761a9f735390
|
704.4 kB | Preview Download |
md5:b1328293415eb2079113530115a57b4d
|
653.5 kB | Preview Download |
md5:e703bd9b68c7b0417453392b5e9dd3d4
|
573.1 kB | Preview Download |
md5:7d4a3677ac48582079e4841e9eea9200
|
660.0 kB | Preview Download |
md5:319eac9e1598fb0ea9954748b48076bc
|
556.9 kB | Preview Download |
md5:fa364e6f2f30f72eaec0fe38d4713020
|
553.7 kB | Preview Download |
md5:5c0ba61e5d68d2f6b344f9f3e0d97fac
|
4.0 MB | Preview Download |