Abstract
Aging causes stem cell dysfunction as a result of extrinsic and intrinsic changes. Decreased function of the stem cell niche is an important contributor to this dysfunction. We use the Drosophila testis to investigate what factors maintain niche cells. The testis niche comprises quiescent “hub” cells and supports two mitotic stem cell pools: germline stem cells and somatic cyst stem cells (CySCs). We identify the cell-cycle-responsive Dp/E2f1 transcription factor as a crucial non-autonomous regulator required in CySCs to maintain hub cell quiescence. Dp/E2f1 inhibits local Activin ligands through production of the Activin antagonist Follistatin (Fs). Inactivation of Dp/E2f1 or Fs in CySCs or promoting Activin receptor signaling in hub cells causes transdifferentiation of hub cells into fully functional CySCs. This Activin-dependent communication between CySCs and hub regulates the physiological decay of the niche with age and demonstrates that hub cell quiescence results from signals from surrounding stem cells.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2284-2294.e6 |
| Journal | Developmental Cell |
| Volume | 56 |
| Issue number | 16 |
| DOIs | |
| State | Published - Aug 23 2021 |
Bibliographical note
Funding Information:For antibodies, the authors acknowledge the DHSB, created by the NICHD of the NIH and maintained at the University of Iowa, Department of Biology, Iowa City, IA 52242, and for plasmids, the authors acknowledge the DGRC at Indiana University, which is supported by a grant from the National Institutes of Health (ORIP and NIGMS). Work in the Bach lab is supported by grants from the NIH and New York State Department of Health/ NYSTEM ( C32584GG ). Work in the Amoyel lab is supported by an Elizabeth Blackwell Institute Early Career Fellowship and an MRC Career Development award MR/P009646/2 .
Funding Information:
The authors thank members of the Bach lab, Jessica Treisman, Hyung Don Ryoo, Vilaiwan Fernandes, Will Wood, Arantza Barrios, and Richard Poole for discussions; Nazif Alic for help with statistics; and Aryeh Korman for help with imaging Babo-GFP. For antibodies, the authors acknowledge the DHSB, created by the NICHD of the NIH and maintained at the University of Iowa, Department of Biology, Iowa City, IA 52242, and for plasmids, the authors acknowledge the DGRC at Indiana University, which is supported by a grant from the National Institutes of Health (ORIP and NIGMS). Work in the Bach lab is supported by grants from the NIH and New York State Department of Health/NYSTEM (C32584GG). Work in the Amoyel lab is supported by an Elizabeth Blackwell Institute Early Career Fellowship and an MRC Career Development award MR/P009646/2. Conceptualization, M.A. and E.A.B.; methodology, S.C.H. M.A. and E.A.B.; validation, M.A. and E.A.B.; formal analysis, S.C.H. M.A. and E.A.B.; investigation, S.C.H. M.A. D.S.d.l.M. L.G. S.M. R.P. and M.B.; resources, M.O. M.A. and E.A.B.; data curation, S.C.H. M.A. and E.A.B.; writing—original draft, S.C.H. M.A. and E.A.B.; writing—review and editing, S.C.H. M.A. and E.A.B.; visualization, S.C.H.; supervision, M.A. and E.A.B.; project administration, M.A. and E.A.B.; funding acquisition, M.A. and E.A.B. The authors declare no competing interests. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science.
Publisher Copyright:
© 2021 The Authors
Keywords
- Activin
- Dp/E2f
- Drosophila
- Follistatin
- aging
- cyst stem cell
- fertility
- niche
- quiescence
- testis
- transdifferentiation