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.

Cellivia 3 S A 61 623 Poznan Poland

Department of Histology and Embryology Poznan University of Medical Sciences 60 781 Poznan Poland

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

Department of Veterinary Surgery Institute of Veterinary Medicine Nicolaus Copernicus University in Torun 87 100 Torun Poland

Division of Anatomy and Histology University of Zielona Góra 65 046 Zielona Góra Poland

Division of Anatomy Department of Human Morphology and Embryology Wroclaw Medical University 50 368 Wroclaw Poland

Division of Histology and Embryology Department of Human Morphology and Embryology Wroclaw Medical University 50 368 Wroclaw Poland

Division of Perinatology and Women's Diseases Poznan University of Medical Sciences 60 535 Poznan Poland

Division of Ultrastructural Research Department of Human Morphology and Embryology Wroclaw Medical University 50 368 Wroclaw Poland

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

Physiology Graduate Faculty North Carolina State University Raleigh NC 27695 USA

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

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Differential regulation of apoptosis-related genes during long-term culture and differentiation of canine adipose-derived stem cells - a functional bioinformatical analysis

Expression Profile of New Marker Genes Involved in Differentiation of Human Wharton's Jelly-Derived Mesenchymal Stem Cells into Chondrocytes, Osteoblasts, Adipocytes and Neural-like Cells