Evidence map›Paper›PMID 37667405›Full record

ArticleGenome medicine2023

Revealing the developmental origin and lineage predilection of neural progenitors within human bone marrow via single-cell analysis: implications for regenerative medicine.

Zhang Changmeng, Wang Hongfei, Martin Chi-Hang Cheung, Ying-Shing Chan, Graham Ka-Hon Shea

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

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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

5 authors at 1 institution in 1 country.

Zhang Changmeng *Department of Orthopaedics and Traumatology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
Wang Hongfei *Department of Orthopaedics and Traumatology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
Martin Chi-Hang CheungSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
Ying-Shing ChanSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
Graham Ka-Hon SheaDepartment of Orthopaedics and Traumatology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong. gkshea@hku.hk.
University of Hong Kong · HK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHuman bone marrow stromal cells (BMSCs) are an easily accessible and expandable progenitor population with the capacity to generate neural cell types in addition to mesoderm. Lineage tracing studies in transgenic animals have indicated Nestin + BMSCs to be descended from the truncal neural crest. Single-cell analysis provides a means to identify the developmental origin and identity of human BMSC-derived neural progenitors when lineage tracing remains infeasible. This is a prerequisite towards translational application.

methodsWe attained transcriptomic profiles of embryonic long bone, adult human bone marrow, cultured BMSCs and BMSC-derived neurospheres. Integrated scRNAseq analysis was supplemented by characterization of cells during culture expansion and following provision of growth factors and signalling agonists to bias lineage.

resultsReconstructed pseudotime upon the integrated dataset indicated distinct neural and osteogenic differentiation trajectories. The starting state towards the neural differentiation trajectory consisted of Nestin + /MKI67 + BMSCs, which could also be diverted towards the osteogenic trajectory via a branch point. Nestin + /PDGFRA + BMSCs responded to neurosphere culture conditions to generate a subpopulation of cells with a neuronal phenotype according to marker expression and gene ontogeny analysis that occupied the end state along the neural differentiation trajectory. Reconstructed pseudotime also revealed an upregulation of BMP4 expression during culture of BMSC-neurospheres. This provided the rationale for culture supplementation with the BMP signalling agonist SB4, which directed progenitors to upregulate Pax6 and downregulate Nestin.

conclusionsThis study suggested BMSCs originating from truncal neural crest to be the source of cells within long bone marrow possessing neural differentiation potential. Unravelling the transcriptomic dynamics of BMSC-derived neural progenitors promises to enhance differentiation efficiency and safety towards clinical application in cell therapy and disease modelling.

Indexed as

Bone MarrowRegenerative MedicineAdultAnimalsHumansNestinNeuronsOsteogenesisNestinBone marrow stromal cellCell differentiationCell lineageNeural crestRegenerative medicineSingle-cell RNA sequencing

Identifiers

PMID37667405
PMCPMC10476295
OpenAlexW4386422244

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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.