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| Status |
Public on Sep 27, 2023 |
| Title |
Single-Cell Multiomics Reveals Distinct Cell States at the Top of the Human Hematopoietic Hierarchy [scATAC-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The advent of single cell (Sc) genomics has challenged the dogma of haematopoiesis as a tree-like structure of stepwise lineage commitment through distinct and increasingly restricted progenitor populations. Instead, analysis of ScRNA-seq has proposed that the earliest events in human hematopoietic stem cell (HSC) differentiation are characterized by only subtle molecular changes, with hematopoietic stem and progenitor cells (HSPCs) existing as a continuum of low-primed cell-states that gradually transition into a specific lineage (CLOUD-HSPCs). Here, we combine ScRNA-seq, ScATAC-seq and cell surface proteomics to dissect the heterogeneity of CLOUD-HSPCs at different stages of human life. Within CLOUD-HSPCs, pseudotime ordering of both mRNA and chromatin data revealed a bifurcation of megakaryocyte/erythroid and lympho/myeloid trajectories immediately downstream a subpopulation with an HSC-specific enhancer signature. Importantly, both HSCs and lineage-restricted progenitor populations could be prospectively isolated based on correlation of their molecular signatures with CD35 and CD11A expression, respectively. Moreover, we describe the changes that occur in this heterogeneity as hematopoiesis develops from neonatal to aged bone marrow, including an increase of HSCs and depletion of lympho-myeloid biased MPPs. Thus, this study dissects the heterogeneity of human CLOUD-HSPCs revealing distinct HSPC-states of relevance in homeostatic settings such as ageing.
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| Overall design |
Singel-Cell ATAC sequencing of hematopoietic stem and progenitors of young bone marrow.
*** The raw data cannot be shared due to EU law (derived from EU patients that are protected by GDPR) ***
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| Contributor(s) |
Sommarin MN, Dhapola P, Karlsson G |
| Citation(s) |
35545037 |
| Submission date |
Apr 22, 2021 |
| Last update date |
Sep 28, 2023 |
| 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 |
| |
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| Platforms (1) |
| GPL24268 |
Illumina Nextseq 500 (Homo sapiens) |
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| Samples (10)
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| This SubSeries is part of SuperSeries: |
| GSE173077 |
Single-Cell Multiomics Reveals Distinct Cell States at the Top of the Human Hematopoietic Hierarchy |
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| Relations |
| BioProject |
PRJNA723752 |
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