A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis
Open accessAbstract
Stromal cells in adult bone marrow that express leptin receptor (LEPR) are a critical source of growth factors, including stem cell factor (SCF), for the maintenance of haematopoietic stem cells and early restricted progenitors 1-6. LEPR+ cells are heterogeneous, including skeletal stem cells and osteogenic and adipogenic progenitors 7-12, although few markers have been available to distinguish these subsets or to compare their functions. Here we show that expression of an osteogenic growth factor, osteolectin 13,14, distinguishes peri-arteriolar LEPR+ cells poised to undergo osteogenesis from peri-sinusoidal LEPR+ cells poised to undergo adipogenesis (but retaining osteogenic potential). Peri-arteriolar LEPR+osteolectin+ cells are rapidly dividing, short-lived osteogenic progenitors that increase in number after fracture and are depleted during ageing. Deletion of Scf from adult osteolectin+ cells did not affect the maintenance of haematopoietic stem cells or most restricted progenitors but depleted common lymphoid progenitors, impairing lymphopoiesis, bacterial clearance, and survival after acute bacterial infection. Peri-arteriolar osteolectin+ cell maintenance required mechanical stimulation. Voluntary running increased, whereas hindlimb unloading decreased, the frequencies of peri-arteriolar osteolectin+ cells and common lymphoid progenitors. Deletion of the mechanosensitive ion channel PIEZO1 from osteolectin+ cells depleted osteolectin+ cells and common lymphoid progenitors. These results show that a peri-arteriolar niche for osteogenesis and lymphopoiesis in bone marrow is maintained by mechanical stimulation and depleted during ageing.
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Reduction in physical activity during ageing may be transmitted via these cells, contributing to a loss of lymphoid progenitors over time.
“Reduction in physical activity during ageing may be transmitted via these cells, contributing to a loss of lymphoid progenitors over time81.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [81]
In the bone marrow, a specialized periarteriolar niche supports lymphoid progenitors and osteogenesis, is maintained by mechanosensation transduced via PIEZO1, is responsive to exercise, and is depleted with ageing, likely contributing to a reduced immune response.
“In the bone marrow, a specialized periarteriolar niche supports lymphoid progenitors and osteogenesis. The niche is maintained by mechanosensation, is transduced via PIEZO1 and is responsive to exercise. This niche is depleted with ageing, likely contributing to a reduced immune response81.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [81]
The HSC niche and lymphoid progenitors can respond positively to exercise.
“However, old HSCs seem to be resistant to the effect of exercise201, although the HSC niche and lymphoid progenitors can respond positively to exercise81.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [81]
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- Authors
- Shen, B., Tasdogan, A., Ubellacker, J. M., Zhang, J., Nosyreva, E. D., Du, L., Murphy, M. M., Hu, S., Yi, Y., Kara, N., Liu, X., Guela, S., Jia, Y., Ramesh, V., Embree, C., Mitchell, E. C., Zhao, Y. C., Ju, L. A., Hu, Z., Crane, G. M., Zhao, Z., Syeda, R., & Morrison, S. J.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Texas A&M University (US)
- The University of Sydney (AU)
- Cleveland Clinic (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Morrison, Sean J.
- ORCID
- Venue
- Nature
- Published
- 2021-02-24
- Volume
- 591
- Issue
- 7850
- Pages
- 438-444
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7979521
- OpenAlex
- W3129753608
- Cited by
- 310
- References
- 50
- Citations by year
- 2026: 52 · 2025: 46 · 2024: 56 · 2023: 54 · 2022: 56 · 2021: 43 · 2020: 3
- FWCI
- 16.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- American Heart Association
- National Heart, Lung, and Blood Institute (F32HL139016)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK118745)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- mesenchymal stem cells, leptin receptor, bone formation, lymphocyte development, common lymphoid progenitors, stem cell factor, hematopoietic stem cells, mechanical stimulation, aging, voluntary running, hindlimb unloading, fracture, adipogenesis, bacterial clearance
- MeSH terms
- Adipose Tissue, Aging, Animals, Arterioles, Bone and Bones, Bone Marrow Cells, Female, Lymphocytes, Male, Osteogenesis, Hematopoietic Cell Growth Factors, Stromal Cells, Stem Cell Factor, Lectins, C-Type, Lymphopoiesis, Mice, Receptors, Leptin, Stem Cell Niche
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