scholarly journals Human Embryonic Stem Cells in Culture Possess Primary Cilia with Hedgehog Signaling Machinery

2008 ◽  
Vol 22 (S1) ◽  
2008 ◽  
Vol 180 (5) ◽  
pp. 897-904 ◽  
Author(s):  
Enko N. Kiprilov ◽  
Aashir Awan ◽  
Romain Desprat ◽  
Michelle Velho ◽  
Christian A. Clement ◽  
...  

Human embryonic stem cells (hESCs) are potential therapeutic tools and models of human development. With a growing interest in primary cilia in signal transduction pathways that are crucial for embryological development and tissue differentiation and interest in mechanisms regulating human hESC differentiation, demonstrating the existence of primary cilia and the localization of signaling components in undifferentiated hESCs establishes a mechanistic basis for the regulation of hESC differentiation. Using electron microscopy (EM), immunofluorescence, and confocal microscopies, we show that primary cilia are present in three undifferentiated hESC lines. EM reveals the characteristic 9 + 0 axoneme. The number and length of cilia increase after serum starvation. Important components of the hedgehog (Hh) pathway, including smoothened, patched 1 (Ptc1), and Gli1 and 2, are present in the cilia. Stimulation of the pathway results in the concerted movement of Ptc1 out of, and smoothened into, the primary cilium as well as up-regulation of GLI1 and PTC1. These findings show that hESCs contain primary cilia associated with working Hh machinery.


2010 ◽  
Vol 3 (2) ◽  
pp. 129-137 ◽  
Author(s):  
Simon C. Weli ◽  
Trine Fink ◽  
Cihan Cetinkaya ◽  
Mayuri S. Prasad ◽  
Cristian P. Pennisi ◽  
...  

2010 ◽  
Vol 4 (1) ◽  
pp. 38-49 ◽  
Author(s):  
Selena Meiyun Wu ◽  
Andre B.H. Choo ◽  
Miranda G.S. Yap ◽  
Ken Kwok-Keung Chan

2021 ◽  
Author(s):  
Sushama Sivakumar ◽  
Shutao Qi ◽  
Ningyan Cheng ◽  
Adwait amod sathe ◽  
Mohammed Kanchwala ◽  
...  

Aneuploidy, defective differentiation, and inactivation of the tumor suppressor TP53 all occur frequently during tumorigenesis. Here, we probe the potential links among these cancer traits by inactivating TP53 in human embryonic stem cells (hESCs). TP53 knockout hESCs exhibit increased proliferation rates, mitotic errors, and low-grade structural aneuploidy; produce poorly differentiated immature teratomas in mice; and fail to differentiate into neural progenitor cells (NPC) in vitro. Genome-wide CRISPR screen reveals requirements of ciliogenesis and sonic hedgehog (Shh) pathways for hESC differentiation into NPCs. TP53 deletion causes abnormal ciliogenesis in neural rosettes. In addition to restraining cell proliferation through CDKN1A, TP53 activates the transcription of BBS9, which encodes a ciliogenesis regulator required for proper Shh signaling and NPC formation. This developmentally regulated transcriptional program of TP53 promotes ciliogenesis, restrains Shh signaling, and commits hESCs to neural lineages.


Stem Cells ◽  
2003 ◽  
Vol 21 (2) ◽  
pp. 131-142 ◽  
Author(s):  
Linzhao Cheng ◽  
Holly Hammond ◽  
Zhaohui Ye ◽  
Xiangcan Zhan ◽  
Gautam Dravid

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