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Single-Cell RNA-Seq Reveals LRRC75A-Expressing Cell Population Involved in VEGF Secretion of Multipotent Mesenchymal
Takumi Miura1,2, Tsukasa Kouno3, Megumi Takano1
1Division of Cell-Based Therapeutic Products, National Institute of Health Sciences, Kanagawa, Japan.
Stem Cells Translational Medicine
|June 1, 2023
Summary
Identifying specific cell subpopulations within mesenchymal stromal/stem cells (MSCs) is crucial for effective cell therapies. This study found leucine-rich repeat-containing 75A (LRRC75A) can identify cells promoting therapeutic angiogenesis.
Area of Science:
- Cell Biology
- Regenerative Medicine
- Biotechnology
Background:
- Human multipotent mesenchymal stromal/stem cells (MSCs) show promise in cell therapy but exhibit heterogeneity, impacting product quality and clinical utility.
- Identifying specific, functional MSC subpopulations is essential to overcome limitations and enhance therapeutic efficacy.
- Angiogenic therapy, crucial for treating ischemic conditions, relies on factors like vascular endothelial growth factor (VEGF) secreted by MSCs.
Purpose of the Study:
- To identify functional cell subpopulations within bone marrow-derived MSCs (BM-MSCs) that predict angiogenic therapy efficacy.
- To investigate the role of specific genes in regulating VEGF secretion in BM-MSCs under ischemic conditions.
- To establish a method for identifying potent angiogenic MSC subpopulations using single-cell analysis.
Main Methods:
- Cultured 11 donor-derived BM-MSC lines under in vitro ischemic conditions to assess VEGF secretion.
- Performed single-cell RNA-sequencing to analyze BM-MSC heterogeneity and identify functional subpopulations.
- Utilized small interfering RNA (siRNA) to knock down leucine-rich repeat-containing 75A (LRRC75A) expression and evaluate its effect on VEGF secretion.
Main Results:
- Significant variation in VEGF secretion was observed among different BM-MSC lines.
- A specific functional cell subpopulation contributing to overall VEGF production under ischemic conditions was identified.
- Leucine-rich repeat-containing 75A (LRRC75A) was found to be highly expressed in this functional subpopulation.
- Knockdown of LRRC75A significantly inhibited VEGF secretion in ischemic BM-MSCs, confirming its regulatory role.
Conclusions:
- LRRC75A serves as a potential biomarker for identifying MSC subpopulations with significant angiogenic potential.
- Single-cell transcriptome profiling is an effective strategy for identifying functional cell subpopulations in heterogeneous MSC products.
- This approach can improve the quality and predictability of MSC-based therapies, particularly for angiogenic applications.
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