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| Status |
Public on Apr 06, 2021 |
| Title |
Multipotent progenitors and hematopoietic stem cells arise independently from hemogenic endothelium in the mouse embryo |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
During embryogenesis, waves of hematopoietic progenitors develop from hemogenic endothelium (HE) prior to the emergence of self-renewing hematopoietic stem cells (HSC). Although previous studies have shown that yolk sac-derived erythromyeloid progenitors and HSC emerge from distinct populations of HE, it remains unknown whether the earliest lymphoid-competent progenitors, multipotent progenitors, and HSC originate from common HE. Here we demonstrate by clonal assays and single cell transcriptomics that rare HE with functional HSC potential in the early murine embryo are distinct from more abundant HE with multilineage hematopoietic potential that fail to generate HSC. Specifically, HSC-competent HE are characterized by expression of CXCR4 surface marker and by higher expression of genes tied to arterial programs regulating HSC dormancy and self-renewal. Together, these findings suggest a revised model of developmental hematopoiesis in which the initial populations of multipotent progenitors and HSC arise independently from HE with distinct phenotypic and transcriptional properties.
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| Overall design |
single cell RNA-sequencing (10X Genomics platform) of murine E9-9.5 P-Sp/AGM-derived FACS-isolated VE-Cadherin+CD61+EPCR+ cells.
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| Contributor(s) |
Hadland B |
| Citation(s) |
34525376 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| K08 HL140143 |
Functional and transcriptional analysis of embryonic hematopoietic stem cell development at the single cell level |
FRED HUTCHINSON CANCER RESEARCH CENTER |
Brandon K Hadland |
| RC2 DK114777 |
Niche signals in HSC genesis |
FRED HUTCHINSON CANCER RESEARCH CENTER |
IRWIN D BERNSTEIN |
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| |
| Submission date |
Apr 05, 2021 |
| Last update date |
Sep 25, 2021 |
| Contact name |
Brandon Hadland |
| E-mail(s) |
bhadland@fredhutch.org
|
| Organization name |
Fred Hutchinson Cancer Research Center
|
| Street address |
1100 Fairview Avenue N., D2-115, P.O. Box 19024
|
| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98109 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA719726 |
| SRA |
SRP313440 |
