Spermatogonial Stem Cell Self-Renewal Requires OCT4, a Factor Downregulated During Retinoic Acid-Induced Differentiation

Stem Cells ◽  
2008 ◽  
Vol 26 (11) ◽  
pp. 2928-2937 ◽  
Author(s):  
Christina Tenenhaus Dann ◽  
Alma L. Alvarado ◽  
Laura A. Molyneux ◽  
Bray S. Denard ◽  
David L. Garbers ◽  
...  
Blood ◽  
2010 ◽  
Vol 116 (2) ◽  
pp. 201-209 ◽  
Author(s):  
Jill L. O. de Jong ◽  
Alan J. Davidson ◽  
Yuan Wang ◽  
James Palis ◽  
Praise Opara ◽  
...  

Abstract Hematopoietic development during embryogenesis involves the interaction of extrinsic signaling pathways coupled to an intrinsic cell fate that is regulated by cell-specific transcription factors. Retinoic acid (RA) has been linked to stem cell self-renewal in adults and also participates in yolk sac blood island formation. Here, we demonstrate that RA decreases gata1 expression and blocks primitive hematopoiesis in zebrafish (Danio rerio) embryos, while increasing expression of the vascular marker, fli1. Treatment with an inhibitor of RA biosynthesis or a retinoic acid receptor antagonist increases gata1+ erythroid progenitors in the posterior mesoderm of wild-type embryos and anemic cdx4−/− mutants, indicating a link between the cdx-hox signaling pathway and RA. Overexpression of scl, a DNA binding protein necessary for hematopoietic development, rescues the block of hematopoiesis induced by RA. We show that these effects of RA and RA pathway inhibitors are conserved during primitive hematopoiesis in murine yolk sac explant cultures and embryonic stem cell assays. Taken together, these data indicate that RA inhibits the commitment of mesodermal cells to hematopoietic fates, functioning downstream of cdx4 and upstream of scl. Our studies establish a new connection between RA and scl during development that may participate in stem cell self-renewal and hematopoietic differentiation.


2010 ◽  
Vol 56 (1) ◽  
pp. 145-153 ◽  
Author(s):  
Mito KANATSU-SHINOHARA ◽  
Narumi OGONUKI ◽  
Hiromi MIKI ◽  
Kimiko INOUE ◽  
Hiroko MORIMOTO ◽  
...  

2017 ◽  
Vol 29 (3) ◽  
pp. 521 ◽  
Author(s):  
Swanand Koli ◽  
Ayan Mukherjee ◽  
Kudumula Venkata Rami Reddy

Restricted availability of retinoic acid (RA) in the testicular milieu regulates transcriptional activity of c-kit (KIT, CD117), which aids in the determination of spermatogonial stem-cell differentiation. The effect of RA on c-kit has been reported previously, but its mode of genomic action remains unresolved. We studied the molecular machinery guiding RA responsiveness to the c-kit gene using spermatogonial stem-cell line C18–4 and primary spermatogonial cells. A novel retinoic acid response element (RARE) positioned at –989 nucleotides upstream of the transcription start site (TSS) was identified, providing a binding site for a dimeric RA receptor (i.e. retinoic acid receptor gamma (RARγ) and retinoic X receptor). RA treatment influenced c-kit promoter activity, along with endogenous c-kit expression in C18–4 cells. A comprehensive promoter deletion assay using the pGL3B reporter system characterised the region spanning –271 bp and –1011 bp upstream of the TSS, which function as minimal promoter and maximal promoter, respectively. In silico analysis predicted that the region –1011 to +58 bp comprised the distal enhancer RARE and activators such as spleen focus forming virus proviral integration oncogene (SPFI1) (PU.1), specificity protein 1 (SP1) and four E26 transformation-specific (ETS) tandem binding sites at the proximal region. Gel retardation and chromatin immunoprecipitation (ChIP) assays showed binding for RARγ, PU.1 and SP1 to the predicted consensus binding sequences, whereas GABPα occupied only two out of four ETS binding sites within the c-kit promoter region. We propose that for RA response, an enhanceosome is orchestrated through scaffolding of a CREB-binding protein (CBP)/p300 molecule between RARE and elements in the proximal promoter region, controlling germ-line expression of the c-kit gene. This study outlines the fundamental role played by RARγ, along with other non-RAR transcription factors (PU.1, SP1 and GABPα), in the regulation of c-kit expression in spermatogonial stem cells in response to RA.


2009 ◽  
Vol 5 (1) ◽  
pp. 76-86 ◽  
Author(s):  
Jiyoung Lee ◽  
Mito Kanatsu-Shinohara ◽  
Hiroko Morimoto ◽  
Yasuhiro Kazuki ◽  
Seiji Takashima ◽  
...  

Development ◽  
2012 ◽  
Vol 139 (10) ◽  
pp. 1734-1743 ◽  
Author(s):  
K. Ishii ◽  
M. Kanatsu-Shinohara ◽  
S. Toyokuni ◽  
T. Shinohara

2017 ◽  
Vol 1 (3) ◽  
pp. 171 ◽  
Author(s):  
Li-Huan Cao ◽  
Xin-Hua Lin ◽  
Qiao-Li Zhang

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