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Somatic support cells restrict germline stem cell self-renewal and promote differentiation

Abstract

Stem cells maintain populations of highly differentiated, short-lived cell-types, including blood, skin and sperm, throughout adult life1. Understanding the mechanisms that regulate stem cell behaviour is crucial for realizing their potential in regenerative medicine2. A fundamental characteristic of stem cells is their capacity for asymmetric division: daughter cells either retain stem cell identity or initiate differentiation. However, stem cells are also capable of symmetric division where both daughters remain stem cells3,4,5,6, indicating that mechanisms must exist to balance self-renewal capacity with differentiation. Here we present evidence that support cells surrounding the stem cells restrict self-renewal and control stem cell number by ensuring asymmetric division. Loss of function of the Drosophila Epidermal growth factor receptor in somatic cells disrupted the balance of self-renewal versus differentiation in the male germline, increasing the number of germline stem cells. We propose that activation of this receptor specifies normal behaviour of somatic support cells; in turn, the somatic cells play a guardian role, providing information that prevents self-renewal of stem cell identity by the germ cell they enclose.

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Figure 1: Three critical decision points in Drosophila early male germ cell differentiation.
Figure 2: Egfr+ restricts proliferation of early germ cells.
Figure 3: Egfr+ restricts germline stem cell self-renewal.
Figure 4: Egfr+ restricts spermatogonial amplification divisions.
Figure 5: Egfr+ activity in somatic cells regulates germline stem cell differentiation.

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Acknowledgements

We thank J. Kumar and K. Moses for the Egfrts allele; S. DiNardo, D. Traver, S. Kim and Fuller lab members for communication of unpublished data and helpful comments; and the Howard Hughes Medical Institute (A.A.K.) and the National Institutes of Health (M.T.F.) for financial support.

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Correspondence to Margaret T. Fuller.

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Kiger, A., White-Cooper, H. & Fuller, M. Somatic support cells restrict germline stem cell self-renewal and promote differentiation. Nature 407, 750–754 (2000). https://doi.org/10.1038/35037606

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