Single cell cortical bone transcriptomics define novel osteolineage gene sets altered in chronic kidney disease
Due to a lack of spatial-temporal resolution at the single cell level, the etiologies of the bone dysfunction caused by diseases such as normal aging, osteoporosis, and the metabolic bone disease associated with chronic kidney disease (CKD) remain largely unknown. To this end, flow cytometry and scR...
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Published in | Frontiers in endocrinology (Lausanne) Vol. 14; p. 1063083 |
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Main Authors | , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
26.01.2023
|
Subjects | |
Online Access | Get full text |
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Summary: | Due to a lack of spatial-temporal resolution at the single cell level, the etiologies of the bone dysfunction caused by diseases such as normal aging, osteoporosis, and the metabolic bone disease associated with chronic kidney disease (CKD) remain largely unknown.
To this end, flow cytometry and scRNAseq were performed on long bone cells from Sost-cre/Ai9
mice, and pure osteolineage transcriptomes were identified, including novel osteocyte-specific gene sets.
Clustering analysis isolated osteoblast precursors that expressed
,
, and
, and a mature osteoblast population defined by
,
, and
. Osteocytes were demarcated by
,
,
,
,
, and
. We validated our
scRNAseq using integrative
promoter occupancy
ATACseq coupled with transcriptomic analyses of a conditional, temporally differentiated MSC cell line. Further, trajectory analyses predicted osteoblast-to-osteocyte transitions
defined pathways associated with a distinct metabolic shift as determined by single-cell flux estimation analysis (scFEA). Using the adenine mouse model of CKD, at a time point prior to major skeletal alterations, we found that gene expression within all stages of the osteolineage was disturbed.
In sum, distinct populations of osteoblasts/osteocytes were defined at the single cell level. Using this roadmap of gene assembly, we demonstrated unrealized molecular defects across multiple bone cell populations in a mouse model of CKD, and our collective results suggest a potentially earlier and more broad bone pathology in this disease than previously recognized. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Ryan C. Riddle, University of Maryland, Baltimore, United States Reviewed by: Alexander Rauch, University of Southern Denmark, Denmark; Satoru Otsuru, University of Maryland, Baltimore, United States This article was submitted to Bone Research, a section of the journal Frontiers in Endocrinology |
ISSN: | 1664-2392 1664-2392 |
DOI: | 10.3389/fendo.2023.1063083 |