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| Status |
Public on Nov 10, 2019 |
| Title |
Neogenin-1 distinguishes between myeloid-biased and balanced Hoxb5+ mouse long-term hematopoietic stem cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Hematopoietic stem cells (HSCs) self-renew and generate all blood cells. Recent studies with single-cell transplants and lineage tracing suggest that adult HSCs are diverse in their reconstitution and lineage potentials. However, prospective isolation of these subpopulations has remained challenging. Here, we identify Neogenin-1 (NEO1) as a unique surface marker on a fraction of mouse HSCs labeled with Hoxb5, a specific reporter of long-term HSCs (LT-HSCs). We show that NEO1+Hoxb5+ LT-HSCs expand with age and respond to myeloablative stress in young mice, while NEO1–Hoxb5+ LT-HSCs exhibit no significant change in number. Furthermore, NEO1+Hoxb5+ LT-HSCs are more often in the G2/S cell cycle phase compared to NEO1–Hoxb5+ LT-HSCs in both young and old bone marrow. Upon serial transplantation, NEO1+Hoxb5+ LT-HSCs exhibit myeloid-biased differentiation and reduced reconstitution, while NEO1–Hoxb5+ LT-HSCs are lineage-balanced and stably reconstitute recipients. Gene expression analysis reveals erythroid and myeloid priming in the NEO1+ fraction and association of quiescence and self-renewal-related transcription factors with NEO1− LT-HSCs. Finally, transplanted NEO1+Hoxb5+ LT-HSCs rarely generate NEO1–Hoxb5+ LT-HSCs, while NEO1–Hoxb5+ LT-HSCs repopulate both LT-HSC fractions. This supports a model in which dormant, balanced, NEO1–Hoxb5+ LT-HSCs can hierarchically precede active, myeloid-biased NEO1+Hoxb5+ LT-HSCs.
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| Overall design |
Bulk RNA-sequencing profiles of NEO1+Hoxb5+ (n = 5) and NEO1–Hoxb5+ (n = 5) LT-HSCs from the bone marrow of 2- to 3-month-old Hoxb5-mCherry mice.
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| Contributor(s) |
Gulati GS, Szade K, Sinha R, Weissman IL |
| Citation(s) |
31754028 |
| Submission date |
Apr 30, 2019 |
| Last update date |
Feb 09, 2020 |
| Contact name |
Gunsagar Singh Gulati |
| E-mail(s) |
gunsagargulati@stanford.edu
|
| Organization name |
Stanford University
|
| Department |
Institute for Stem Cell Biology and Regenerative Medicine
|
| Lab |
Irving Weissman
|
| Street address |
265 Campus Drive
|
| City |
Palo Alto |
| State/province |
CA |
| ZIP/Postal code |
94305 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA540492 |
| SRA |
SRP194273 |
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