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Apoptosis in the Fetal Testis Eliminates Developmentally Defective Germ Cell Clones

36 Pages Posted: 30 Apr 2019 Publication Status: Review Complete

See all articles by Daniel H. Nguyen

Daniel H. Nguyen

University of California, San Francisco (UCSF) - Department of Obstetrics, Gynecology and Reproductive Sciences; University of California, San Francisco (UCSF) - Center for Reproductive Sciences; University of California, San Francisco (UCSF) - Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research

Diana J. Laird

University of California, San Francisco (UCSF) - Department of Obstetrics, Gynecology and Reproductive Sciences; University of California, San Francisco (UCSF) - Center for Reproductive Sciences; University of California, San Francisco (UCSF) - Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research

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Abstract

Many germ cells (GCs) are eliminated during development, long before differentiating to egg or sperm, but it is not clear why. Here, we examined how GC composition in the mouse fetal testis is altered by scheduled apoptosis during sex differentiation. Multicolored-lineage tracing revealed that apoptosis affects clonally-related GCs, suggesting that this fate decision occurs autonomously based on shared intrinsic properties. We identified extensive transcriptional heterogeneity among fetal GCs including an apoptosis-susceptible subpopulation delineated by high Trp53 and deviant differentiation. Alternatively, the GC subpopulation most likely to survive was advanced in differentiation. These results indicate that GC developmental fate is based upon discrete and cell-heritable fitnesses and imply that a dichotomy between sex-differentiation and apoptosis coordinates the removal of developmentally incompetent cells to improve gamete quality. Evidence that GC subpopulations are in different epigenetic states suggests that errors in epigenetic reprogramming form the basis of aberrant differentiation and apoptotic selection.

Keywords: selection; clone; male differentiation; apoptosis; LINE1; transposon, epigenetics; cell heterogeneity; germ cell

Suggested Citation

Nguyen, Daniel H. and Laird, Diana J., Apoptosis in the Fetal Testis Eliminates Developmentally Defective Germ Cell Clones (April 25, 2019). Available at SSRN: https://ssrn.com/abstract=3378004 or http://dx.doi.org/10.2139/ssrn.3378004
This version of the paper has not been formally peer reviewed.

Daniel H. Nguyen

University of California, San Francisco (UCSF) - Department of Obstetrics, Gynecology and Reproductive Sciences

San Francisco, CA 94143
United States

University of California, San Francisco (UCSF) - Center for Reproductive Sciences

San Francisco, CA
United States

University of California, San Francisco (UCSF) - Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research

San Francisco, CA
United States

Diana J. Laird (Contact Author)

University of California, San Francisco (UCSF) - Department of Obstetrics, Gynecology and Reproductive Sciences ( email )

San Francisco, CA 94143
United States

University of California, San Francisco (UCSF) - Center for Reproductive Sciences ( email )

San Francisco, CA
United States

University of California, San Francisco (UCSF) - Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research ( email )

San Francisco, CA
United States

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