|
| Status |
Public on Mar 08, 2021 |
| Title |
Differential chromatin binding of the lung lineage transcription factor NKX2-1 resolves opposing murine alveolar cell fates in vivo [ATAC-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Differential use of identical DNA sequences leads to distinct tissue lineages and then multiple cell types within a lineage, an epigenetic process central to progenitor and stem cell biology. The associated genomic changes, especially in native tissues, remain insufficiently understood, and are hereby addressed in the mouse lung, where the same lineage transcription factor NKX2-1 promotes the diametrically opposed alveolar type 1 (AT1) versus AT2 cell fate. We show that the cell-type-specific function of NKX2-1 is attributed to its differential chromatin binding that is acquired or retained during development in coordination with partner transcriptional factors. Loss of YAP/TAZ redirects NKX2-1 from its AT1-specific to AT2-specific binding sites, leading to transcriptionally exaggerated AT2 cells when deleted in progenitors or AT1-to-AT2 conversion when deleted after fate commitment. Nkx2-1 mutant AT1 and AT2 cells gain distinct accessible sites including those of the opposite fate while adopting the gastrointestinal fate, suggesting an epigenetic plasticity larger than a transcriptional one. Our genomic analysis of single or purified cells, coupled with precision genetics, provides an epigenetic roadmap of alveolar cell fate and potential, and introduces an experimental benchmark for unraveling the in vivo function of lineage transcription factors.
|
| |
|
| Overall design |
FACS-purified lung epithelial, immune, endothelial, and mesenchymal cells were processed through the Chromium Single Cell Gene Expression Solution Platform (10X Genomics)
|
| |
|
| Contributor(s) |
Little D, Chen J |
| Citation(s) |
33947861, 38755149 |
| |
| Submission date |
Sep 16, 2020 |
| Last update date |
May 29, 2024 |
| Contact name |
Danielle R. Little |
| E-mail(s) |
Danielle.Little@stjude.org
|
| Phone |
9015953487
|
| Organization name |
St. Jude Children's Research Hospital
|
| Department |
Developmental Neurobiology
|
| Lab |
Michael Dyer
|
| Street address |
262 Danny Thomas Pl Rm D2031
|
| City |
Memphis |
| State/province |
Tennessee |
| ZIP/Postal code |
38105 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (9)
|
|
| This SubSeries is part of SuperSeries: |
| GSE158205 |
Differential chromatin binding of the lung lineage transcription factor NKX2-1 resolves opposing murine alveolar cell fates in vivo |
|
| Relations |
| BioProject |
PRJNA663783 |
| SRA |
SRP282565 |
Less...
More...