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Microfluidic single-cell transcriptional analysis rationally identifies novel surface marker profiles to enhance cell-based therapies

Robert C. Rennert, Michael Januszyk, Michael Sorkin, Melanie Rodrigues, Zeshaan N. Maan, Dominik Duscher, Alexander J. Whittam, Revanth Kosaraju, Michael T. Chung, Kevin Paik, Alexander Y. Li, Michael Findlay, Jason P. Glotzbach, Atul J. Butte and Geoffrey C. Gurtner ()
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Robert C. Rennert: Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine
Michael Januszyk: Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine
Michael Sorkin: Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine
Melanie Rodrigues: Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine
Zeshaan N. Maan: Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine
Dominik Duscher: Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine
Alexander J. Whittam: Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine
Revanth Kosaraju: Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine
Michael T. Chung: Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine
Kevin Paik: Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine
Alexander Y. Li: Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine
Michael Findlay: Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine
Jason P. Glotzbach: Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine
Atul J. Butte: Stanford University School of Medicine
Geoffrey C. Gurtner: Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine

Nature Communications, 2016, vol. 7, issue 1, 1-9

Abstract: Abstract Current progenitor cell therapies have only modest efficacy, which has limited their clinical adoption. This may be the result of a cellular heterogeneity that decreases the number of functional progenitors delivered to diseased tissue, and prevents correction of underlying pathologic cell population disruptions. Here, we develop a high-resolution method of identifying phenotypically distinct progenitor cell subpopulations via single-cell transcriptional analysis and advanced bioinformatics. When combined with high-throughput cell surface marker screening, this approach facilitates the rational selection of surface markers for prospective isolation of cell subpopulations with desired transcriptional profiles. We establish the usefulness of this platform in costly and highly morbid diabetic wounds by identifying a subpopulation of progenitor cells that is dysfunctional in the diabetic state, and normalizes diabetic wound healing rates following allogeneic application. We believe this work presents a logical framework for the development of targeted cell therapies that can be customized to any clinical application.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11945

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DOI: 10.1038/ncomms11945

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