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| Status |
Public on Jul 16, 2019 |
| Title |
Myeloid Skewing in Aging Bone Marrow Depends on Long-lived Plasma Cell Accumulation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Aging results in a reduction in B lymphopoiesis and an increase in myelopoiesis in mice and humans. We investigated how cellular changes in the aging hematopoietic microenvironment contribute to these alterations in hematopoiesis and found that long-lived plasma cells (LLPCs) increase in number in the bone marrow of old mice. The LLPCs exhibited a Toll Like Receptor activation signal, and their accumulation was partially dependent on inflammatory cytokines. LLPCs were able to stimulate myelopoiesis from hematopoietic stem cells and myeloid progenitors in vitro, and anti-CD138 antibody-mediated depletion of LLPCs or blockade of pro-inflammatory signaling in old mice in vivo resulted in a significant reduction in LLPC number and attenuated myeloid development. However, B lymphopoiesis remained suppressed. These data identify the increase in LLPC number as obligate for age-associated increases in myelopoiesis and provide evidence that, in the context of aging, enhanced myelopoiesis and depressed lymphopoiesis are distinct, independently regulated processes.
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| Overall design |
We isolated bone marrow long-lived plasma cells (LLPCs) as CD45R(B220)- IgD- CD138high TCRb- TCRgd- CD11b- Gr-1- from three independent groups of young (2-3 months, female) and old (17-19 months, male) mice and performed RNA-Seq.
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| Contributor(s) |
Pioli PD, Montecino-Rodriguez E, Casero D, Morrison SL, Dorshkind K |
| Citation(s) |
31303400 |
| Submission date |
Apr 10, 2018 |
| Last update date |
Jul 16, 2019 |
| Contact name |
Kenneth Dorshkind |
| E-mail(s) |
kdorshki@mednet.ucla.edu
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| Phone |
310 206-9535
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| Organization name |
David Geffen School of Medicine at UCLA
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| Department |
Pathology and Laboratory Medicine
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| Street address |
10833 Le Conte Avenue
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| City |
Los Angeles |
| State/province |
California |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (1) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA449533 |
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