|
| Status |
Public on Sep 16, 2022 |
| Title |
scNMT-seq of the adult NSC lineage - MAB-seq |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
|
| Summary |
Stem cells in the adult brain are specialized astrocytes capable of generating neurons and glial cells. While neural stem cells (NSCs) and common astrocytes have clearly distinct functions, they share highly similar transcriptome profiles. How stemness is molecularly encoded is therefore unclear. Here we use single-cell NMT-seq to simultaneously characterize the transcriptome, DNA methylome and chromatin accessibility of astrocytes and the NSC lineage in the healthy and ischemic brain. Our data reveal distinct methylation profiles associated with either astrocyte or stem cell function. Stemness is conferred by methylation of astrocyte genes and demethylation of neurogenic genes that are expressed only later. Surprisingly, ischemic injury unlocks the stemness-methylome in common astrocytes enabling generation of neuroblasts. Furthermore, we show that oligodendrocytes employ Tet-mediated demethylation to regulate expression of myelin-related genes, many of which are abnormally methylated in multiple sclerosis. Overall, we show that DNA methylation is a promising target for regenerative medicine.
|
| |
|
| Overall design |
Oligodendrocytes, neuroblasts and adult neural stem cells/astrocytes were isolated via flourescence-activated cell sorting (FACS) from the ventricular-subventricular zone. Each biological replicate consists of 10.000-20.000 cells from 12 pooled mice. Samples were subjected to MAB-seq in order to detect remnants of active demethylation via TET enzymes.
|
| |
|
| Contributor(s) |
Kremer LP, Cerrizuela S, Eid Al Shukairi M, Ellinger T, Straub J, Dehler S, Korkmaz A, Weichenhan D, Plass C, Anders S, Martin-Villalba A |
| Citation(s) |
36072757 |
| |
| Submission date |
Aug 22, 2022 |
| Last update date |
Sep 17, 2022 |
| Contact name |
Ana Martin-Villalba |
| Organization name |
German Cancer Research Center
|
| Department |
Molecular Neurobiology
|
| Street address |
Im Neuenheimer Feld 280
|
| City |
Heidelberg |
| ZIP/Postal code |
69121 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (6)
|
|
| This SubSeries is part of SuperSeries: |
| GSE210806 |
Single-cell triple-omics uncovers DNA methylation as key feature of stemness in the healthy and ischemic adult brain |
|
| Relations |
| BioProject |
PRJNA872120 |
Less...
More...