Single cell transcriptomics identifies a unique adipose lineage cell population that regulates bone marrow environment
- University of Pennsylvania, United States
- The Children's Hospital of Philadelphia, United States
Abstract
Bone marrow mesenchymal lineage cells are a heterogeneous cell population involved in bone homeostasis and diseases such as osteoporosis. While it is long postulated that they originate from mesenchymal stem cells, the true identity of progenitors and their in vivo bifurcated differentiation routes into osteoblasts and adipocytes remain poorly understood. Here, by employing large scale single cell transcriptome analysis, we computationally defined mesenchymal progenitors at different stages and delineated their bi-lineage differentiation paths in young, adult and aging mice. One identified subpopulation is a unique cell type that expresses adipocyte markers but contains no lipid droplets. As non-proliferative precursors for adipocytes, they exist abundantly as pericytes and stromal cells that form a ubiquitous 3D network inside the marrow cavity. Functionally they play critical roles in maintaining marrow vasculature and suppressing bone formation. Therefore, we name them marrow adipogenic lineage precursors (MALPs) and conclude that they are a new component of marrow adipose tissue.
Data availability
Sequencing data have been deposited in GEO under accession code GSE145477
-
Single cell transcriptomics analysis of bone marrow mesenchymal lineage cellsNCBI Gene Expression Omnibus, GSE145477.
-
Bone marrow nicheNCBI Gene Expression Omnibus, GSE108892.
Article and author information
Author details
Funding
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR066098)
- Ling Qin
National Institutes of Health (R03DE028026)
- Chider Chen
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK095803)
- Ling Qin
Penn Center for Musculoskeletal Disorders (P30AR069619)
- Ling Qin
National Institutes of Health (R21AR074570)
- Ling Qin
American Heart Association (17GRNT33650029)
- Yanqing Gong
National Institutes of Health (R01HL095675)
- Wei Tong
National Institutes of Health (R01HL133828)
- Wei Tong
Nihon University (F31HL139091)
- Nicholas Holdreith
National Institute of Dental and Craniofacial Research (R00DE025915)
- Chider Chen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal work performed in this report was approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Pennsylvania under Protocol 804112. University Laboratory Animal Resources (ULAR) of the University of Pennsylvania is responsible for the procurement, care, and use of all university-owned animals as approved by IACUC. Animal facilities in the University of Pennsylvania meet federal, state, and local guidelines for laboratory animal care and are accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care International.
Copyright
© 2020, Zhong et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 18,519
- views
-
- 2,737
- downloads
-
- 249
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Single cell transcriptomics identifies a unique adipose lineage cell population that regulates bone marrow environment
eLife 9:e54695.
https://doi.org/10.7554/eLife.54695
Further reading
-
- Cell Biology
- Developmental Biology
A study in mice reveals key interactions between proteins involved in fibroblast growth factor signaling and how they contribute to distinct stages of eye lens development.
-
- Cell Biology
- Evolutionary Biology
Maintenance of rod-shape in bacterial cells depends on the actin-like protein MreB. Deletion of mreB from Pseudomonas fluorescens SBW25 results in viable spherical cells of variable volume and reduced fitness. Using a combination of time-resolved microscopy and biochemical assay of peptidoglycan synthesis, we show that reduced fitness is a consequence of perturbed cell size homeostasis that arises primarily from differential growth of daughter cells. A 1000-generation selection experiment resulted in rapid restoration of fitness with derived cells retaining spherical shape. Mutations in the peptidoglycan synthesis protein Pbp1A were identified as the main route for evolutionary rescue with genetic reconstructions demonstrating causality. Compensatory pbp1A mutations that targeted transpeptidase activity enhanced homogeneity of cell wall synthesis on lateral surfaces and restored cell size homeostasis. Mechanistic explanations require enhanced understanding of why deletion of mreB causes heterogeneity in cell wall synthesis. We conclude by presenting two testable hypotheses, one of which posits that heterogeneity stems from non-functional cell wall synthesis machinery, while the second posits that the machinery is functional, albeit stalled. Overall, our data provide support for the second hypothesis and draw attention to the importance of balance between transpeptidase and glycosyltransferase functions of peptidoglycan building enzymes for cell shape determination.
