|
| Status |
Public on May 02, 2022 |
| Title |
Concurrent stem- and lineage-affiliated chromatin programs precede hematopoietic lineage restriction |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
|
| Summary |
The emerging notion of hematopoietic stem- and progenitor cells (HSPCs) as a low-primed cloud without sharply demarcated gene expression programs raises the question on how cellular fate options emerge, and at which stem-like stage lineage priming is initiated. Here we investigated single-cell chromatin accessibility of Lineage-, cKit+, Sca1+ (LSK) HSPCs spanning the early differentiation landscape. Application of a signal-processing algorithm to detect transition points corresponding to massive alterations in accessibility of 521 transcription factor-motifs revealed a population of LSK FMS-like tyrosine kinase 3(Flt3)intCD9high cells that concurrently display stem-like and lineage-affiliated chromatin signatures pointing to simultaneous gain of both Lympho-Myeloid and Megakaryocyte-Erythroid programs. Molecularly and functionally, these cells position between stem cells and committed progenitors, display multi-lineage capacity in vitro and in vivo, but lack self-renewal activity. This integrative molecular analysis resolves the heterogeneity of cells along hematopoietic differentiation trajectories, and permits investigation of chromatin-mediated transition between multipotency and lineage restriction.
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| |
|
| Overall design |
Single-cell ATAC-Seq and single cell RNA-Seq
|
| Web link |
https://doi.org/10.1016/j.celrep.2022.110798
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| |
|
| Contributor(s) |
Safi F, Dhapola P, Thakur R, Karlsson G |
| Citation missing |
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| BioProject |
PRJNA625393 |
| |
| Submission date |
Apr 15, 2020 |
| Last update date |
May 04, 2022 |
| Contact name |
Göran Karlsson |
| E-mail(s) |
goran.karlsson@med.lu.se
|
| Phone |
+46 462221261
|
| Organization name |
Lund University
|
| Department |
Division of Molecular Hematology
|
| Lab |
Stem cells and leukemia lab
|
| Street address |
Kilinkgatan 26 BMC B12
|
| City |
Lund |
| State/province |
Scania |
| ZIP/Postal code |
221 84 |
| Country |
Sweden |
| |
|
| Platforms (2) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (11)
|
|
| Relations |
| SRA |
SRP256408 |
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