Apoptosis Related Human Wharton’s Jelly-Derived Stem Cells Differentiation into Osteoblasts, Chondrocytes, Adipocytes and Neural-like Cells—Complete Transcriptomic Assays

Author:

Stefańska Katarzyna12ORCID,Nemcova Lucie3ORCID,Blatkiewicz Małgorzata1ORCID,Pieńkowski Wojciech4,Ruciński Marcin1ORCID,Zabel Maciej56,Mozdziak Paul7ORCID,Podhorska-Okołów Marzenna8,Dzięgiel Piotr5ORCID,Kempisty Bartosz9101112

Affiliation:

1. Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland

2. Cellivia 3 S.A., 61-623 Poznan, Poland

3. Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, 27721 Libechov, Czech Republic

4. Division of Perinatology and Women’s Diseases, Poznan University of Medical Sciences, 60-535 Poznan, Poland

5. Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland

6. Division of Anatomy and Histology, University of Zielona Góra, 65-046 Zielona Góra, Poland

7. Prestage Department of Poultry Sciences, North Carolina State University, Raleigh, NC 27695, USA

8. Division of Ultrastructural Research, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland

9. Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland

10. Division of Anatomy, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland

11. Department of Obstetrics and Gynecology, University Hospital and Masaryk University, 60177 Brno, Czech Republic

12. Physiology Graduate Faculty, North Carolina State University, Raleigh, NC 27695, USA

Abstract

Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) exhibit multilineage differentiation potential, adhere to plastic, and express a specific set of surface markers—CD105, CD73, CD90. Although there are relatively well-established differentiation protocols for WJ-MSCs, the exact molecular mechanisms involved in their in vitro long-term culture and differentiation remain to be elucidated. In this study, the cells were isolated from Wharton’s jelly of umbilical cords obtained from healthy full-term deliveries, cultivated in vitro, and differentiated towards osteogenic, chondrogenic, adipogenic and neurogenic lineages. RNA samples were isolated after the differentiation regimen and analyzed using an RNA sequencing (RNAseq) assay, which led to the identification of differentially expressed genes belonging to apoptosis-related ontological groups. ZBTB16 and FOXO1 were upregulated in all differentiated groups as compared to controls, while TGFA was downregulated in all groups. In addition, several possible novel marker genes associated with the differentiation of WJ-MSCs were identified (e.g., SEPTIN4, ITPR1, CNR1, BEX2, CD14, EDNRB). The results of this study provide an insight into the molecular mechanisms involved in the long-term culture in vitro and four-lineage differentiation of WJ-MSCs, which is crucial to utilize WJ-MSCs in regenerative medicine.

Funder

Polish Ministry of Science and Higher Education

Ministry of Education, Youth and Sports of the Czech Republic

National Institute of Food and Agriculture

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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