scholarly journals Marker expression reveals heterogeneity of spermatogonia in the neonatal mouse testis

Reproduction ◽  
2015 ◽  
Vol 149 (4) ◽  
pp. 329-338 ◽  
Author(s):  
Bryan A Niedenberger ◽  
Jonathan T Busada ◽  
Christopher B Geyer
Keyword(s):  
Stem Cell ◽  
Retinoic Acid ◽  
Cell Fate ◽  
Normal Development ◽  
Type A ◽  
Spermatogonial Stem Cell ◽  
Differentiation Markers ◽  
Undifferentiated State ◽  
Neonatal Testis ◽  
Type A Spermatogonia

Prospermatogonia transition to type A spermatogonia, which provide the source for the spermatogonial stem cell (SSC) pool. A percentage of these type A spermatogonia then differentiate to enter meiosis as spermatocytes by ∼P10. It is currently unclear as to when these distinct populations are initially formed in the neonatal testis, and when the expression of markers both characteristic of and required for the adult undifferentiated and differentiating states is established. In this study, we compared expression of known spermatogonial cell fate markers during normal development and in response to the differentiation signal provided by retinoic acid (RA). We found that some markers for the undifferentiated state (ZBTB16/PLZF and CDH1) were expressed in nearly all spermatogonia from P1 through P7. In contrast, differentiation markers (STRA8 and KIT) appeared in a subset of spermatogonia at P4, coincident with the onset of RA signaling. GFRA1, which was present in nearly all prospermatogonia at P1, was only retained in STRA8/KIT− spermatogonia. From P4 through P10, there was a great deal of heterogeneity in the male germ cell population in terms of expression of markers, as markers characteristic of the undifferentiated (except GFRA1) and differentiating states were co-expressed through this interval. After P10, these fate markers diverged to mark distinct populations of undifferentiated and differentiating spermatogonia, and this pattern was maintained in juvenile (P18) and adult (P>60) testes. Taken together, these results reveal that the spermatogonia population is heterogeneous during the first wave of spermatogenesis, and indicate that neonatal spermatogonia may not serve as an ideal substitute for studying the function of adult spermatogonia.

scholarly journals Interaction of retinoic acid and scl controls primitive blood development

Blood ◽  
2010 ◽  
Vol 116 (2) ◽  
pp. 201-209 ◽  
Author(s):  
Jill L. O. de Jong ◽  
Alan J. Davidson ◽  
Yuan Wang ◽  
James Palis ◽  
Praise Opara ◽  
...  
Keyword(s):  
Stem Cell ◽  
Retinoic Acid ◽  
Cell Fate ◽  
Embryonic Stem ◽  
Yolk Sac ◽  
Erythroid Progenitors ◽  
Self Renewal ◽  
Hematopoietic Development ◽  
Blood Island ◽  
Primitive Hematopoiesis

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.

335 Divergent VEGFA signaling determines spermatogonial stem cell fate

2016 ◽  
Vol 94 (suppl_2) ◽  
pp. 157-158
Author(s):  
K. M. Sargent ◽  
J. R. Essink ◽  
M. L. Bremer ◽  
W. E. Pohlmeier ◽  
M. M. Laughlin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Spermatogonial Stem Cell ◽  
Stem Cell Fate

scholarly journals Stem cell activity of type A spermatogonia is seasonally regulated in rainbow trout†

2017 ◽  
Vol 96 (6) ◽  
pp. 1303-1316 ◽  
Author(s):  
Mana Sato ◽  
Makoto Hayashi ◽  
Goro Yoshizaki
Keyword(s):  
Stem Cell ◽  
Rainbow Trout ◽  
Cell Activity ◽  
Type A ◽  
Stem Cell Activity ◽  
Type A Spermatogonia

Retinoic acid triggers c-kit gene expression in spermatogonial stem cells through an enhanceosome constituted between transcription factor binding sites for retinoic acid response element (RARE), spleen focus forming virus proviral integration oncogene (SPFI1) (PU.1) and E26 transformation-specific (ETS)

2017 ◽  
Vol 29 (3) ◽  
pp. 521 ◽  
Author(s):  
Swanand Koli ◽  
Ayan Mukherjee ◽  
Kudumula Venkata Rami Reddy
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Retinoic Acid ◽  
Binding Sites ◽  
Promoter Region ◽  
Spermatogonial Stem Cell ◽  
Proviral Integration ◽  
Response Element ◽  
Retinoic Acid Response Element ◽  
Kit Gene

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.

STK31 acts as a cell fate determinant in spermatogonial stem cell

2010 ◽  
Vol 34 (8) ◽  
pp. S37-S37
Author(s):  
Kin Lam Ellis Fok ◽  
Chin Man Chung ◽  
Hsiao Chang Chan
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Spermatogonial Stem Cell ◽  
Cell Fate Determinant ◽  
A Cell

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 ◽  
...  
Keyword(s):  
Stem Cell ◽  
Retinoic Acid ◽  
Spermatogonial Stem Cell ◽  
Induced Differentiation ◽  
Self Renewal

scholarly journals Ectopic POU5F1 in the male germ lineage disrupts differentiation and spermatogenesis in mice

Reproduction ◽  
2016 ◽  
Vol 152 (4) ◽  
pp. 363-377 ◽  
Author(s):  
Yu Zheng ◽  
LeAnna J Phillips ◽  
Rachel Hartman ◽  
Junhui An ◽  
Christina T Dann
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Germ Cells ◽  
Progenitor Cell ◽  
Ectopic Expression ◽  
Transgenic Mouse Model ◽  
Spermatogonial Stem Cell ◽  
Early Embryogenesis ◽  
Cell Lineages ◽  
Progenitor Cell Population

Expression levels of the pluripotency determinant, POU5F1, are tightly regulated to ensure appropriate differentiation during early embryogenesis. POU5F1 is also present in the spermatogonial stem cell/progenitor cell population in mice and it is downregulated as spermatogenesis progresses. To test if POU5F1 downregulation is required for SSCs to differentiate, we produced transgenic mice that ubiquitously express POU5F1 in Cre-expressing lineages. Using a Vasa-Cre driver to produce ectopic POU5F1 in all postnatal germ cells, we found that POU5F1 downregulation was necessary for spermatogonial expansion during the first wave of spermatogenesis and for the production of differentiated spermatogonia capable of undergoing meiosis. In contrast, undifferentiated spermatogonia were maintained throughout adulthood, consistent with a normal presence of POU5F1 in these cells. The results suggest that POU5F1 downregulation in differentiating spermatogonia is a necessary step for the progression of spermatogenesis. Further, the creation of a transgenic mouse model for conditional ectopic expression of POU5F1 may be a useful resource for studies of POU5F1 in other cell lineages, during tumorogenesis and cell fate reprogramming.

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