Research article

The pluripotency factor LIN28 marks undifferentiated spermatogonia in mouse

Ke Zheng¹ , Xin Wu¹ , Klaus H Kaestner² and Peijing Jeremy Wang¹

¹Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA

²Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA

author email corresponding author email

BMC Developmental Biology 2009, 9:38doi:10.1186/1471-213X-9-38

Published:	29 June 2009

Abstract

Background

Life-long production of spermatozoa depends on spermatogonial stem cells. Spermatogonial stem cells exist among the most primitive population of germ cells – undifferentiated spermatogonia. Transplantation experiments have demonstrated the functional heterogeneity of undifferentiated spermatogonia. Although the undifferentiated spermatogonia can be topographically divided into A_s (single), A_pr (paired), and A_al (aligned) spermatogonia, subdivision of this primitive cell population using cytological markers would greatly facilitate characterization of their functions.

Results

In the present study, we show that LIN28, a pluripotency factor, is specifically expressed in undifferentiated spermatogonia (A_s, A_pr, and A_al) in mouse. Ngn3 also specifically labels undifferentiated spermatogonia. We used Ngn3-GFP knockin mice, in which GFP expression is under the control of all Ngn3 transcription regulatory elements. Remarkably, Ngn3-GFP is only expressed in ~40% of LIN28-positive A_s (single) cells. The percentage of Ngn3-GFP-positive clusters increases dramatically with the chain length of interconnected spermatogonia.

Conclusion

Our study demonstrates that LIN28 specifically marks undifferentiated spermatogonia in mice. These data, together with previous studies, suggest that the LIN28-expressing undifferentiated spermatogonia exist as two subpopulations: Ngn3-GFP-negative (high stem cell potential) and Ngn3-GFP-positive (high differentiation commitment). Furthermore, Ngn3-GFP-negative cells are found in chains of Ngn3-GFP-positive spermatogonia, suggesting that cells in the A_al spermatogonia could revert to a more primitive state.