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| Status |
Public on Jan 03, 2018 |
| Title |
Clonal analysis of lineage fate in unperturbed hematopoiesis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The classical tenet of hematopoiesis posits well-accepted lineage trees that arise from progressively restricted oligopotent and unipotent progenitor populations. However, because fate in hematopoiesis has mostly been studied in the context of transplantation, it is unclear whether these lineage branches and such proposed oligopotent progenitors exist in an unperturbed hematopoietic system. Here, we utilize endogenous transposon tagging to trace the fate of thousands of progenitors and stem cells over time to re-evaluate these dogmas. Our results describe a novel clonal roadmap where the megakaryocyte lineage arises independently of lymphoid and myeloid/erythroid fates. Our data also demonstrate that true oligopotency is largely restricted to the multipotent progenitor (MPP) compartment. Analysis of thousands of stem cell and progenitor transcriptomes demonstrates that lineage determination starts at the MPP stage and identifies a functional hierarchy within this population that drives hematopoiesis. Finally, our results demonstrate that long-term hematopoietic stem cells behave physiologically as megakaryocyte lineage progenitors. Our data provide evidence for a substantially revised hematopoietic roadmap, and highlights unique properties of MPPs and HSCs in situ.
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| Overall design |
Single-cell mRNA sequencing of hematopoietic stem cells and multipotent progenitor subsets from mouse bone marrow. Sample LTHSC represents 940 single cells. Sample MPP2 represents 776 single cells. Sample MPP3 represents 1372 single cells. Sample MPP4 represents 1016 single cells. Sample STHSC represents 837 single cells.
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| Contributor(s) |
Rodriguez-Fraticelli AE, Wolock S, Weinreb CS, Jankovic M, Sun J, Klein AM, Camargo F |
| Citation(s) |
29323290, 32025033 |
| |
| Submission date |
Dec 01, 2016 |
| Last update date |
Feb 19, 2020 |
| Contact name |
Fernando Camargo |
| E-mail(s) |
Fernando.Camargo@childrens.harvard.edu
|
| Organization name |
Boston Children's Hospital
|
| Department |
Stem Cell and Regenerative Biology
|
| Street address |
300 Longwood Ave
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA355645 |
| SRA |
SRP094420 |
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