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| Status |
Public on Apr 26, 2018 |
| Title |
Single-cell epigenomics maps the continuous regulatory landscape of human hematopoietic differentiation [bulk ATAC-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Normal human hematopoiesis involves cellular differentiation of multipotent cells into progressively more lineage-restricted states. While epigenomic landscapes of this process have been explored in immunophenotypically-defined populations, the single-cell regulatory variation that defines hematopoietic differentiation has been hidden by ensemble averaging. We generated single-cell chromatin accessibility landscapes across 8 populations of immunophenotypically-defined human hematopoietic cell types. Using bulk chromatin accessibility profiles to scaffold our single-cell data analysis, we constructed an epigenomic landscape of human hematopoiesis and characterized epigenomic heterogeneity within phenotypically sorted populations to find epigenomic lineage-bias toward different developmental branches in multipotent stem cell states. We identify and isolate sub-populations within classically-defined granulocyte-macrophage progenitors (GMPs) and use ATAC-seq and RNA-seq to confirm that GMPs are epigenomically and transcriptomically heterogeneous. Furthermore, we identified transcription factors and cis-regulatory elements linked to changes in chromatin accessibility within cellular populations and across a continuous myeloid developmental trajectory, and observe relatively simple TF motif dynamics give rise to a broad diversity of accessibility dynamics at cis-regulatory elements. Overall, this work provides a template for exploration of complex regulatory dynamics in primary human tissues at the ultimate level of granular specificity – the single cell.
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| |
|
| Overall design |
Profiles of bulk epigenomes, assayed using ATAC-seq, across sorted cell types from CD34+ bone marrow.
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| |
|
| Contributor(s) |
Buenrostro J |
| Citation(s) |
29706549 |
| Submission date |
Mar 17, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Jason Daniel Buenrostro |
| E-mail(s) |
jdbuenrostro@gmail.com
|
| Organization name |
Broad Institute
|
| Street address |
415 Main Street
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (13)
|
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| This SubSeries is part of SuperSeries: |
| GSE96772 |
Single-cell epigenomics maps the continuous regulatory landscape of human hematopoietic differentiation |
|
| Relations |
| BioProject |
PRJNA379614 |
| SRA |
SRP102090 |
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