Uric acid: a potent molecular contributor to pluripotent stem cell cardiac differentiation via mesoderm specification
Authors: Bingbing Ke
Zhihong Zhao
Feng Lan
Anila Khalique
James Chong
Wen-Jing Lu
Fusheng Han
Hua He
Taoyan Liu
Jingyi Wang
Yujie Zeng
Journal: Cell Death and Differentiation (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Congenital heart disease; cardiomyocytes; pluripotent stem cells; uric acid; cardiac differentiation
Affiliations: Department of Emergency Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China., Department of Cardiology, ZhouPu Hospital, PuDong New Area District, Shanghai, 200120, China., Department of Ultrasound, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China., Beijing Lab for Cardiovascular Precision Medicine, Anzhen Hospital, Capital Medical University, Beijing, 10029, China., Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, Hawkesbury Rd, Westmead, NSW, 2145, Australia., Department of Cardiology, Westmead Hospital, Hawkesbury Rd, Westmead, NSW, 2145, Australia., Beijing Lab for Cardiovascular Precision Medicine, Anzhen Hospital, Capital Medical University, Beijing, 10029, China. ., Department of Emergency Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China. .

Abstract:  Congenital heart disease (CHD) is the most common cause of congenital anomaly and a leading cause of morbidity and mortality worldwide. Generation of cardiomyoctyes derived from pluripotent stem cells (PSCs) has opened new avenues for investigation of human cardiac development. Here we report that uric acid (UA), a physiologically abundant compound during embryonic development, can consistently and robustly enhance cardiac differentiation of human PSCs including hESCs and hiPSCs, in replacement of ascorbic acid (AA). We optimized treatment conditions and demonstrate that differentiation day 0-2, a period for specification of mesoderm cells, was a critical time for UA effects. This was further confirmed by UA-induced upregulation of mesodermal markers. Furthermore, we show that the developing mesoderm may be by directly promoted by SNAI pathway-mediated epithelial-mesenchymal transition (EMT) at 0-24 h and a lengthened G0/G1 phase by increasing the ubiquitination degradation in 24-48 h. These findings demonstrate that UA plays a critical role in mesoderm differentiation, and its level might be a useful indicator for CHD in early fetal ultrasound screening. 

Retracted: No

PubPeer comments:
 Some images in Figure 1A appear to overlap, although the horizontal dimensions seem different. *** Closeup ![file] *** ![file] , 
 In the article titled: Uric acid: a potent molecular contributor to pluripotent stem cell cardiac differentiation via mesoderm specification (Cell Death Differ, 2019 May;26(5):826-842), the authors had wrongly put a same image as Figure 1A 10mg dl into the place of Figure 1A 30mg dl duo to editing error during manuscript preparation. Now we have corrected it and the wrong image has been removed and the right image has been inserted in the place of Figure 1A 30mg dl in the corrected Figure 1. , 
 We have wrote to the editorial office of the journal, to sent a statement correcting the error. , 
 #3 Thank you. Could the authors provide a copy of the correct figure here? Also what is the explanation for the dimensions being different without affecting the scale bars? , 
 Yesterday I could not succeed to upload the corrected Figure 1 in the clipboard after having tried a few times. We will try to upload it again. , 
 #5 An alternative method: upload to image sharing site like bitly and post a link here. , 
 #4 ![file] ,