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Publication : A regulatory role for CHD4 in maintenance of the spermatogonial stem cell pool.

First Author  Cafe SL Year  2021
Journal  Stem Cell Reports Volume  16
Issue  6 Pages  1555-1567
PubMed ID  33961790 Mgi Jnum  J:333260
Mgi Id  MGI:6813994 Doi  10.1016/j.stemcr.2021.04.003
Citation  Cafe SL, et al. (2021) A regulatory role for CHD4 in maintenance of the spermatogonial stem cell pool. Stem Cell Reports 16(6):1555-1567
abstractText  Maintenance and self-renewal of the spermatogonial stem cell (SSC) population is the cornerstone of male fertility. Here, we have identified a key role for the nucleosome remodeling protein CHD4 in regulating SSC function. Gene expression analyses revealed that CHD4 expression is highly enriched in the SSC population in the mouse testis. Using spermatogonial transplantation techniques it was established that loss of Chd4 expression significantly impairs SSC regenerative capacity, causing a approximately 50% reduction in colonization of recipient testes. An scRNA-seq comparison revealed reduced expression of "self-renewal" genes following Chd4 knockdown, along with increased expression of signature progenitor genes. Co-immunoprecipitation analyses demonstrated that CHD4 regulates gene expression in spermatogonia not only through its traditional association with the remodeling complex NuRD, but also via interaction with the GDNF-responsive transcription factor SALL4. Cumulatively, the results of this study depict a previously unappreciated role for CHD4 in controlling fate decisions in the spermatogonial pool.
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