The role of Dnmt3L in maintaining the property of spermatogonial stem cells during mouse germ cell development
Date Issued
2011
Date
2011
Author(s)
Shou-Cheng Chen, Wendy
Abstract
Epigenetic regulation of gene activities is crucial for proper cellular function. Some of the stem cells in vivo are kept in a quiescent status, waiting for their turn to proliferate or differentiate. DNA methyl- transferase 3-like (Dnmt3L) is a very important epigenetic regulator expressed during germ line development. Deficiency of Dnmt3L in male germ cells causes severe hypomethylation in retrotransposons. This leads to germ cell depletion after the pachytene stage and eventually sertoli-cell only syndrome in mice. However, how Dnmt3L affects the function of spermatogonial progenitor/stem cells (SSCs) is not well understood. This study focuses on the developmental stages of SSCs in mice, and investigates the role of Dnmt3L in maintaining SSCs property.
The first part of the study showed that Dnmt3L was essential for the establishment and/or maintenance of the quiescent status of SSCs. It was concluded from the reduced Plzf positive cells and perinuclear staining pattern of two heterochromatin markers H3K9me3 and H4K20me3 in Dnmt3L-/- neonatal mice testes. Our preliminary functional transplantation study also demonstrated that Dnmt3L-/- spermatogonia could not colonize the wild-type host testes. Taken together, the first part of the study has demonstrated a new role of Dnmt3L on keeping the quiescent status of SSCs. Also, Dnmt3L seems to be an epigenetic regulator not only important for DNA methylation, but also involved in proper heterochromatin establishment and/or maintenance in SSCs. The second part of this study showed that deficiency of Dnmt3L may affect the niche environment essential for sustain in the normal function of SSCs. Based on Vasa and Stra8 staining patterns, we’ve observed an abnormal germ cell-niche/somatic cell segregation, the niche structure that was supposed to hold the spermatogonia seemed to be disrupted in Dnmt3L-/- 5 wks-old testes. Preliminary functional transplantation studies also demonstrated that Dnmt3L-/- testes failed to support the colonization repopulation of wild-type spermatogonia. The second part of our study gives a hint that Dnmt3L is not only essential for germ cell function, but may also affect normal niche environment that supports SSCs.
In conclusion, this study has used SSCs as a model to connect the epigenetic modifier Dnmt3L from DNA methylation to histone modification. Also, functional analysis and molecular staining demonstrate that Dnmt3L is not only necessary for normal SSC function, but may also directly or indirectly maintain the niche environment of SSCs.
Subjects
Dnmt3L
spermatogonial stem cells
mice
epigenetics
histone modification
testis transplantation
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