Abstract

Mesenchymal stromal cells (MSCs) have great value in cell therapies. The MSC therapies have many challenges due to its inconsistent potency and limited quantity. Here, we report a strategy to generate induced MSCs (iMSCs) by directly reprogramming human peripheral blood mononuclear cells (PBMCs) with OCT4, SOX9, MYC, KLF4, and BCL-XL using a nonintegrating episomal vector system. While OCT4 was not required to reprogram PBMCs into iMSCs, omission of OCT4 significantly impaired iMSC functionality. The omission of OCT4 resulted in significantly downregulating MSC lineage specific and mesoderm-regulating genes, including SRPX, COL5A1, SOX4, SALL4, TWIST1. When reprogramming PBMCs in the absence of OCT4, 67 genes were significantly hypermethylated with reduced transcriptional expression. These data indicate that transient expression of OCT4 may serve as a universal reprogramming factor by increasing chromatin accessibility and promoting demethylation. Our findings represent an approach to produce functional MSCs, and aid in identifying putative function associated MSC markers.

Induced MSCs (iMSCs) are generated by direct reprogramming of human PBMCs using 5 factor transfection, including OCT4, SOX9, MYC, KLF4, and BCL-XL.

Details

Title
Reprogramming of human peripheral blood mononuclear cells into induced mesenchymal stromal cells using non-integrating vectors
Author
Chen, Wanqiu 1 ; Wang, Chenguang 2 ; Yang, Zhi-Xue 3 ; Zhang, Feng 3 ; Wen, Wei 3 ; Schaniel, Christoph 4   VIAFID ORCID Logo  ; Mi, Xianqiang 5 ; Bock, Matthew 6   VIAFID ORCID Logo  ; Zhang, Xiao-Bing 7   VIAFID ORCID Logo  ; Qiu, Hongyu 8   VIAFID ORCID Logo  ; Wang, Charles 9   VIAFID ORCID Logo 

1  Loma Linda University, Center for Genomics, School of Medicine, Loma Linda, USA (GRID:grid.43582.38) (ISNI:0000 0000 9852 649X) 
2  Loma Linda University, Center for Genomics, School of Medicine, Loma Linda, USA (GRID:grid.43582.38) (ISNI:0000 0000 9852 649X); Shanghai Institute of Microsystem and Information Technology Chinese Academy of Sciences, Shanghai, China (GRID:grid.458459.1) (ISNI:0000 0004 1792 5798) 
3  Loma Linda University, Department of Medicine, Loma Linda, USA (GRID:grid.43582.38) (ISNI:0000 0000 9852 649X); State Key Laboratory of Experimental Hematology, Tianjin, China (GRID:grid.43582.38) 
4  Black Family Stem Cell Institute, Tisch Cancer Institute, Mount Sinai Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinai, Division of Hematology and Medical Oncology, New York, USA (GRID:grid.516104.7) (ISNI:0000 0004 0408 1530) 
5  Shanghai Institute of Microsystem and Information Technology Chinese Academy of Sciences, Shanghai, China (GRID:grid.458459.1) (ISNI:0000 0004 1792 5798) 
6  Loma Linda University, Department of Pediatrics, School of Medicine, Loma Linda, USA (GRID:grid.43582.38) (ISNI:0000 0000 9852 649X) 
7  Loma Linda University, Department of Medicine, Loma Linda, USA (GRID:grid.43582.38) (ISNI:0000 0000 9852 649X) 
8  University of Arizona - College of Medicine at Phoenix, Translational Cardiovascular Research Center, Department of Internal Medicine, Phoenix, USA (GRID:grid.134563.6) (ISNI:0000 0001 2168 186X) 
9  Loma Linda University, Center for Genomics, School of Medicine, Loma Linda, USA (GRID:grid.43582.38) (ISNI:0000 0000 9852 649X); Loma Linda University, Division of Microbiology & Molecular Genetics, Department of Basic Sciences, School of Medicine, Loma Linda, USA (GRID:grid.43582.38) (ISNI:0000 0000 9852 649X) 
Pages
393
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
23993642
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s42003-023-04737-x
ProQuest document ID
2799317098
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.