Evidence map›Paper›PMID 34737845›Full record

ArticleOxidative medicine and cellular longevity2021

Single-Cell Integration Analysis of Heterotopic Ossification and Fibrocartilage Developmental Lineage: Endoplasmic Reticulum Stress Effector Xbp1 Transcriptionally Regulates the Notch Signaling Pathway to Mediate Fibrocartilage Differentiation.

Yisheng Chen, Yaying Sun, Yuzhen Xu, Wei-Wei Lin, Zhiwen Luo, Zhihua Han, Shaohua Liu, Beijie Qi, Chenyu Sun, Ken Go and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Oxidative medicine and cellular longevity, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
5.3field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Deciphering the Regulatory Networks of the Migrasome-Associated Cell Subpopulation in Heterotopic Ossification via Multi-Omics Analysis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Metabolic Syndrome and Tendon Disease: A Comprehensive Review.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 3 countries.

Yisheng ChenDepartment of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China.ORCID https://orcid.org/0000-0001-6498-7519
Yaying SunDepartment of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Yuzhen XuDepartment of Rehabilitation, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong Province 271000, China.ORCID https://orcid.org/0000-0002-1289-3438
Wei-Wei LinDepartment of Neurosurgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009 Zhejiang, China.ORCID https://orcid.org/0000-0001-8304-9659
Zhiwen LuoDepartment of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Zhihua HanDepartment of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China.
Shaohua LiuDepartment of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Beijie QiDepartment of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Chenyu SunInternal Medicine, AMITA Health Saint Joseph Hospital Chicago, 2900 N. Lake Shore Drive, Chicago, 60657 Illinois, USA.
Ken GoDepartment of Clinical Training Centre, St. Marianna Hospital, Tokyo, Japan.
X-R KangShanghai Jiao Tong University, Shanghai 200080, China.
Jiwu ChenDepartment of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China.ORCID https://orcid.org/0000-0002-5063-3629
Fudan University · CNShanghai Jiao Tong University · CNAffiliated Hospital of Taishan Medical University · CNSaint Joseph Hospital · USSecond Affiliated Hospital of Zhejiang University · CNSt. Marianna University School of Medicine · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionRegeneration of fibrochondrocytes is essential for the healing of the tendon-bone interface (TBI), which is similar to the formation of neurogenic heterotopic ossification (HO). Through single-cell integrative analysis, this study explored the homogeneity of HO cells and fibrochondrocytes.

methodsThis study integrated six datasets, namely, GSE94683, GSE144306, GSE168153, GSE138515, GSE102929, and GSE110993. The differentiation trajectory and key transcription factors (TFs) for HO occurrence were systematically analyzed by integrating single-cell RNA (scRNA) sequencing, bulk RNA sequencing, and assay of transposase accessible chromatin seq. The differential expression and enrichment pathways of TFs in heterotopically ossified tissues were identified.

resultsHO that mimicked pathological cells was classified into HO1 and HO2 cell subsets. Results of the pseudo-temporal sequence analysis suggested that HO2 is a differentiated precursor cell of HO1. The analysis of integrated scRNA data revealed that ectopically ossified cells have similar transcriptional characteristics to cells in the fibrocartilaginous zone of tendons. The modified SCENIC method was used to identify specific transcriptional regulators associated with ectopic ossification. Xbp1 was defined as a common key transcriptional regulator of ectopically ossified tissues and the fibrocartilaginous zone of tendons. Subsequently, the CellPhoneDB database was completed for the cellular ligand-receptor analysis. With further pathway screening, this study is the first to propose that Xbp1 may upregulate the Notch signaling pathway through Jag1 transcription. Twenty-four microRNAs were screened and were found to be potentially associated with upregulation of XBP1 expression after acute ischemic stroke.

conclusionA systematic analysis of the differentiation landscape and cellular homogeneity facilitated a molecular understanding of the phenotypic similarities between cells in the fibrocartilaginous region of tendon and HO cells. Furthermore, by identifying Xbp1 as a hub regulator and by conducting a ligand-receptor analysis, we propose a potential Xbp1/Jag1/Notch signaling pathway.

Indexed as

Endoplasmic Reticulum StressAnimalsBone and BonesCell DifferentiationCell LineageFibrocartilageGene Expression ProfilingHumansMaleMiceMice, Inbred C57BLOssification, HeterotopicOsteogenesisReceptors, NotchSingle-Cell AnalysisX-Box Binding Protein 1Receptors, NotchX-Box Binding Protein 1XBP1 protein, human

Identifiers

PMID34737845
PMCPMC8563124
OpenAlexW3208590320

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.