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Home / Equine Research Bank / Stem Cell Res Ther / Single-cell RNA sequencing of equine mesenchymal stromal cel...
Stem cell research & therapy2020; 11(1); 524; doi: 10.1186/s13287-020-02043-5

Single-cell RNA sequencing of equine mesenchymal stromal cells from primary donor-matched tissue sources reveals functional heterogeneity in immune modulation and cell motility.

Abstract: The efficacy of mesenchymal stromal cell (MSC) therapy is thought to depend on the intrinsic heterogeneity of MSC cultures isolated from different tissue sources as well as individual MSCs isolated from the same tissue source, neither of which is well understood. To study this, we used MSC cultures isolated from horses. The horse is recognized as a physiologically relevant large animal model appropriate for translational MSC studies. Moreover, due to its large size the horse allows for the simultaneous collection of adequate samples from multiple tissues of the same animal, and thus, for the unique collection of donor matched MSC cultures from different sources. The latter is much more challenging in mice and humans due to body size and ethical constraints, respectively. In the present study, we performed single-cell RNA sequencing (scRNA-seq) on primary equine MSCs that were collected from three donor-matched tissue sources; adipose tissue (AT), bone marrow (BM), and peripheral blood (PB). Based on transcriptional differences detected with scRNA-seq, we performed functional experiments to examine motility and immune regulatory function in distinct MSC populations. We observed both inter- and intra-source heterogeneity across the three sources of equine MSCs. Functional experiments demonstrated that transcriptional differences correspond with phenotypic variance in cellular motility and immune regulatory function. Specifically, we found that (i) differential expression of junctional adhesion molecule 2 (JAM2) between MSC cultures from the three donor-matched tissue sources translated into altered cell motility of BM-derived MSCs when RNA interference was used to knock down this gene, and (ii) differences in C-X-C motif chemokine ligand 6 (CXCL6) expression in clonal MSC lines derived from the same tissue source correlated with the chemoattractive capacity of PB-derived MSCs. Ultimately, these findings will enhance our understanding of MSC heterogeneity and will lead to improvements in the therapeutic potential of MSCs, accelerating the transition from bench to bedside.
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Publication Date: 2020-12-04 PubMed ID: 33276815PubMed Central: PMC7716481DOI: 10.1186/s13287-020-02043-5Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study examines mesenchymal stromal cell (MSC) cultures isolated from different tissue sources in horses using single-cell RNA sequencing, revealing crucial differences in cell motility and immune modulation. The variations at the transcriptional level correspond with differing phenotypic traits and functionalities of the cells.

Methodology and Sample Collection

  • The research team centered their examination around horses, a large animal model that facilitates the collection of ample samples from varying tissues from the same specimen. This arrangement is scarcely possible in mice or humans due to size constraints and ethical reasons, respectively.
  • The study involved primary equine MSCs collated from three distinct tissues within the same animal, namely adipose tissue (AT), bone marrow (BM), and peripheral blood (PB).

Single-cell RNA Sequencing and Functional Experiments

  • Each MSC was subjected to single-cell RNA sequencing (scRNA-seq), keenly observing for transcriptional differences therein.
  • Following this, functional experiments were conducted to examine cellular motility and immune regulatory function in the different MSC populations.

Findings and Observations

  • The study found heterogeneity both within (intra) and between (inter) the three different sources of equine MSCs.
  • Functional experiments revealed that the observed transcriptional differences correspond with phenotypic variance in terms of cell motility and immune regulatory function.
  • There was a noted differential expression of the junctional adhesion molecule 2 (JAM2) between MSC cultures from the three tissue sources. This translated into altered cell motility of bone marrow-derived MSCs when RNA interference was used to suppress the JAM2 gene.
  • Differences in the expression of C-X-C motif chemokine ligand 6 (CXCL6) in clonal MSC lines from the same tissue source corresponded with the chemoattractive capacity of peripheral blood-derived MSCs.

Implications of the Study

  • This research elucidates our understanding of MSC heterogeneity and highlights the potential for enhancing MSC therapeutic impact by focusing on specific tissue-derived MSCs. This could eventually accelerate the transition of MSC research from lab-based investigations to practical, clinical applications.

Cite This Article

APA
Harman RM, Patel RS, Fan JC, Park JE, Rosenberg BR, Van de Walle GR. (2020). Single-cell RNA sequencing of equine mesenchymal stromal cells from primary donor-matched tissue sources reveals functional heterogeneity in immune modulation and cell motility. Stem Cell Res Ther, 11(1), 524. https://doi.org/10.1186/s13287-020-02043-5

Publication

Stem cell research & therapy
ISSN: 1757-6512
NlmUniqueID: 101527581
Country: England
Language: English
Volume: 11
Issue: 1
Pages: 524
PII: 524

Researcher Affiliations

Harman, Rebecca M
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
Patel, Roosheel S
  • Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Fan, Jennifer C
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
Park, Jee E
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
Rosenberg, Brad R
  • Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Van de Walle, Gerlinde R
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA. grv23@cornell.edu.

MeSH Terms

  • Animals
  • Bone Marrow Cells
  • Cell Differentiation
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Horses
  • Mesenchymal Stem Cells
  • Mice
  • Sequence Analysis, RNA

Conflict of Interest Statement

The authors declare no competing interests.

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