WNT3 is a biomarker capable of predicting the definitive endoderm differentiation potential of hESCs.
Generation of functional cells from human pluripotent stem cells (PSCs) through in vitro differentiation is a promising approach for drug screening and cell therapy. However, the observed large and unavoidable variation in the differentiation potential of different human embryonic stem cell (hESC)/induced PSC (iPSC) lines makes the selection of an appropriate cell line for the differentiation of a particular cell lineage difficult. Here, we report identification of WNT3 as a biomarker capable of predicting definitive endoderm (DE) differentiation potential of hESCs. We show that the mRNA level of WNT3 in hESCs correlates with their DE differentiation efficiency. In addition, manipulations of hESCs through WNT3 knockdown or overexpression can respectively inhibit or promote DE differentiation in a WNT3 level-dependent manner. Finally, analysis of several hESC lines based on their WNT3 expression levels allowed accurate prediction of their DE differentiation potential. Collectively, our study supports the notion that WNT3 can serve as a biomarker for predicting DE differentiation potential of hESCs.
Howard Hughes Medical Institute, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA ; Program in Cellular and Molecular Medicine, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA ; Division of Hematology/Oncology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
Wei
W
Jiang
Donghui
D
Zhang
Nenad
N
Bursac
Yi
Y
Zhang
D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D004707:Endoderm / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060508:Wnt3 Protein / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D012333:RNA, Messenger; C555507:WNT3 protein, human; D060508:Wnt3 Protein