Evidence map›Paper›PMID 33473154›Full record

ArticleCell research2021

Dissecting human embryonic skeletal stem cell ontogeny by single-cell transcriptomic and functional analyses.

Jian He, Jing Yan, Jianfang Wang, Liangyu Zhao, Qian Xin, Yang Zeng, Yuxi Sun, Han Zhang, Zhijie Bai, Zongcheng Li and 11 more

Open access · hybridAbstract read
In one paragraph

Article in Cell research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed
13.2field-weighted citation impact, top 1% 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

77 citing papers in PubMed, 131 citations in OpenAlex.

  1. Review
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  5. Endothelin-1/endothelin B receptor signalling mediates Prx1Journal of orthopaedic translation · 2026
    Article
  6. Bridging skeletal stem cell diversity and human skeletal modeling.Journal of bone and mineral metabolism · 2026
    Review
  7. Article
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  20. Modulation of senescent LeprStem cell research & therapy · 2025
    Article

17 more citing papers are in PubMed but not listed here.

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

21 authors at 9 institutions in 1 country.

Jian He *State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, 100071, China.
Jing Yan *State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, 100071, China.
Jianfang Wang *Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
Liangyu Zhao *Department of Orthopedics, Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
Qian Xin *State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, 100071, China.
Yang ZengState Key Laboratory of Experimental Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, China.
Yuxi SunDepartment of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
Han ZhangDepartment of Transfusion, Daping Hospital, Army Military Medical University, Chongqing, 400042, China.
Zhijie BaiState Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, 100071, China.ORCID http://orcid.org/0000-0003-2231-1320
Zongcheng LiState Key Laboratory of Experimental Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, China.ORCID http://orcid.org/0000-0002-5189-5268
Yanli NiState Key Laboratory of Experimental Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, China.
Yandong GongState Key Laboratory of Experimental Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, China.
Yunqiao LiState Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, 100071, China.
Han HeState Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, 100071, China.
Zhilei BianDepartment of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.ORCID http://orcid.org/0000-0003-0680-4029
Yu LanKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, Guangdong, 510632, China.ORCID http://orcid.org/0000-0002-4731-5945
Chunyu MaDepartment of Gynecology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, China.
Lihong BianDepartment of Gynecology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, China.
Heng ZhuBeijing Institute of Radiation Medicine, Beijing, 100850, China. zhudingdingabc@163.com.
Bing LiuState Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, 100071, China. bingliu17@yahoo.com.ORCID http://orcid.org/0000-0002-7313-6924
Rui YueInstitute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China. ryue@tongji.edu.cn.ORCID http://orcid.org/0000-0002-3401-369X
Academy of Military Medical Sciences · CNChinese PLA General Hospital · CNJinan University · CNTongji University · CNBeijing Radiation Center · CNDaping Hospital · CNFirst Affiliated Hospital of Zhengzhou University · CNShanghai Changzheng Hospital · CNShanghai East Hospital · CN

Funding

National Natural Science Foundation of China (National Science Foundation of China) 31425012National Natural Science Foundation of China (National Science Foundation of China) 81871771National Natural Science Foundation of China (National Science Foundation of China) 81890991,31871173
6 · The paper itself

Abstract

Human skeletal stem cells (SSCs) have been discovered in fetal and adult long bones. However, the spatiotemporal ontogeny of human embryonic SSCs during early skeletogenesis remains elusive. Here we map the transcriptional landscape of human limb buds and embryonic long bones at single-cell resolution to address this fundamental question. We found remarkable heterogeneity within human limb bud mesenchyme and epithelium, and aligned them along the proximal-distal and anterior-posterior axes using known marker genes. Osteo-chondrogenic progenitors first appeared in the core limb bud mesenchyme, which give rise to multiple populations of stem/progenitor cells in embryonic long bones undergoing endochondral ossification. Importantly, a perichondrial embryonic skeletal stem/progenitor cell (eSSPC) subset was identified, which could self-renew and generate the osteochondral lineage cells, but not adipocytes or hematopoietic stroma. eSSPCs are marked by the adhesion molecule CADM1 and highly enriched with FOXP1/2 transcriptional network. Interestingly, neural crest-derived cells with similar phenotypic markers and transcriptional networks were also found in the sagittal suture of human embryonic calvaria. Taken together, this study revealed the cellular heterogeneity and lineage hierarchy during human embryonic skeletogenesis, and identified distinct skeletal stem/progenitor cells that orchestrate endochondral and intramembranous ossification.

Indexed as

OsteogenesisTranscriptomeCell DifferentiationForkhead Transcription FactorsHumansMesodermRepressor ProteinsSkullStem CellsForkhead Transcription FactorsFOXP1 protein, humanRepressor Proteins

Identifiers

PMID33473154
PMCPMC8249634
OpenAlexW3124098591

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.