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Single cell RNA sequence analysis of human bone marrow samples reveals new targets for isolation of skeletal stem cells using DNA-coated gold nanoparticles

Single cell RNA sequence analysis of human bone marrow samples reveals new targets for isolation of skeletal stem cells using DNA-coated gold nanoparticles
Single cell RNA sequence analysis of human bone marrow samples reveals new targets for isolation of skeletal stem cells using DNA-coated gold nanoparticles
There is a wealth of data indicating human bone marrow derived stromal cells (HBMSCs) contain the skeletal stem cell (SSC) with the potential to differentiate along the stromal osteogenic, adipogenic and chondrogenic lineages. However, despite these advances, current methods to isolate skeletal stem cells (SSCs) from human tissues have proved challenging as no single specific marker has been identified limiting understanding of SSC fate, immunophenotype and the widespread clinical application of these cells. While a number of cell surface markers can enrich for SSCs, none of the proposed markers, alone, provide a platform to isolate single cells with the ability to form bone, cartilage, and adipose tissue in humans. The current study details the application of oligonucleotide-coated nanoparticles, spherical nucleic acids (SNAs), to rapidly isolate human cells using mRNAs signatures detected in SSCs in real time, to identify stem and progenitor skeletal populations using single cell RNA sequencing. Based on scRNA-seq of samples from 11 patients, this method was able to identify novel targets for SSC enrichment, which were assessed in a total of 80 patients. This methodology was able to isolate potential SSCs found at a frequency of <1 in 1,000,000 in human bone marrow, with a capacity for tri-lineage differentiation in vitro. The current approach provides new targets and a platform to advance SSC isolation, enrichment with significant therapeutic impact therein.
2041-7314
Matthews, Elloise Zena
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Lanham, Stuart
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White, Kate
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Kyriazi, Maria-Eleni
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Alexaki, Konstantina
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El-Sagheer, Afaf H.
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Brown, Tom
2816825b-9f1a-40c7-b7f0-2c660b702cc1
Kanaras, Antonios
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West, Jonathan
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Macarthur, Benjamin
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Stumpf, Patrick S.
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Oreffo, Richard
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Matthews, Elloise Zena
11178b9e-5173-4db3-8606-3ce4a5688e7f
Lanham, Stuart
28fdbbef-e3b6-4fdf-bd0f-4968eeb614d6
White, Kate
ad592ed1-c133-4e3a-abed-3803a6d5531c
Kyriazi, Maria-Eleni
01916df9-2aa2-424e-9e58-4d0db900e456
Alexaki, Konstantina
5cb992a9-d06e-494a-bfff-7d298881bf2e
El-Sagheer, Afaf H.
44c25cbd-405e-4e8f-aa12-443536a67f0d
Brown, Tom
2816825b-9f1a-40c7-b7f0-2c660b702cc1
Kanaras, Antonios
667ecfdc-7647-4bd8-be03-a47bf32504c7
West, Jonathan
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Macarthur, Benjamin
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Stumpf, Patrick S.
9ad6d7ee-68e6-4272-b735-d7d7a9050ca4
Oreffo, Richard
ff9fff72-6855-4d0f-bfb2-311d0e8f3778

Matthews, Elloise Zena, Lanham, Stuart, White, Kate, Kyriazi, Maria-Eleni, Alexaki, Konstantina, El-Sagheer, Afaf H., Brown, Tom, Kanaras, Antonios, West, Jonathan, Macarthur, Benjamin, Stumpf, Patrick S. and Oreffo, Richard (2023) Single cell RNA sequence analysis of human bone marrow samples reveals new targets for isolation of skeletal stem cells using DNA-coated gold nanoparticles. Journal of Tissue Engineering. (doi:10.1101/2020.06.17.156836). (In Press)

Record type: Article

Abstract

There is a wealth of data indicating human bone marrow derived stromal cells (HBMSCs) contain the skeletal stem cell (SSC) with the potential to differentiate along the stromal osteogenic, adipogenic and chondrogenic lineages. However, despite these advances, current methods to isolate skeletal stem cells (SSCs) from human tissues have proved challenging as no single specific marker has been identified limiting understanding of SSC fate, immunophenotype and the widespread clinical application of these cells. While a number of cell surface markers can enrich for SSCs, none of the proposed markers, alone, provide a platform to isolate single cells with the ability to form bone, cartilage, and adipose tissue in humans. The current study details the application of oligonucleotide-coated nanoparticles, spherical nucleic acids (SNAs), to rapidly isolate human cells using mRNAs signatures detected in SSCs in real time, to identify stem and progenitor skeletal populations using single cell RNA sequencing. Based on scRNA-seq of samples from 11 patients, this method was able to identify novel targets for SSC enrichment, which were assessed in a total of 80 patients. This methodology was able to isolate potential SSCs found at a frequency of <1 in 1,000,000 in human bone marrow, with a capacity for tri-lineage differentiation in vitro. The current approach provides new targets and a platform to advance SSC isolation, enrichment with significant therapeutic impact therein.

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Accepted/In Press date: 24 March 2023
Additional Information: . For the purpose of open access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.

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Local EPrints ID: 476836
URI: http://eprints.soton.ac.uk/id/eprint/476836
ISSN: 2041-7314
PURE UUID: 406eebe5-187b-4d95-805d-eb2af134c231
ORCID for Stuart Lanham: ORCID iD orcid.org/0000-0002-4516-264X
ORCID for Antonios Kanaras: ORCID iD orcid.org/0000-0002-9847-6706
ORCID for Jonathan West: ORCID iD orcid.org/0000-0002-5709-6790
ORCID for Benjamin Macarthur: ORCID iD orcid.org/0000-0002-5396-9750
ORCID for Richard Oreffo: ORCID iD orcid.org/0000-0001-5995-6726

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Date deposited: 17 May 2023 16:43
Last modified: 17 Mar 2024 03:29

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Contributors

Author: Elloise Zena Matthews
Author: Stuart Lanham ORCID iD
Author: Kate White
Author: Maria-Eleni Kyriazi
Author: Konstantina Alexaki
Author: Afaf H. El-Sagheer
Author: Tom Brown
Author: Jonathan West ORCID iD
Author: Patrick S. Stumpf
Author: Richard Oreffo ORCID iD

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