Regulation of Self-renewal and Differentiation in Adult Stem Cell Lineages: Lessons from the Drosophila Male Germ Line

5-Methylcytosine (m5C) is a RNA modification that exists in tRNAs and rRNAs and was recently found in mRNAs. Although it has been suggested to regulate diverse biological functions, whether m5C RNA modification influences adult stem cell development remains undetermined. In this study, we show that Ypsilon schachtel (YPS), a homolog of human Y box binding protein 1 (YBX1), promotes germ line stem cell (GSC) maintenance, proliferation, and differentiation in the Drosophila ovary by preferentially binding to m5C-containing RNAs. YPS is genetically demonstrated to function intrinsically for GSC maintenance, proliferation, and progeny differentiation in the Drosophila ovary, and human YBX1 can functionally replace YPS to support normal GSC development. Highly conserved cold-shock domains (CSDs) of YPS and YBX1 preferentially bind to m5C RNA in vitro. Moreover, YPS also preferentially binds to m5C-containing RNAs, including mRNAs, in germ cells. The crystal structure of the YBX1 CSD-RNA complex reveals that both hydrophobic stacking and hydrogen bonds are critical for m5C binding. Overexpression of RNA-binding–defective YPS and YBX1 proteins disrupts GSC development. Taken together, our findings show that m5C RNA modification plays an important role in adult stem cell development.

Download Full-text

Loss of foxo rescues stem cell aging in Drosophila germ line

eLife ◽

10.7554/elife.27842 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 8

Author(s):

Filippo Artoni ◽

Rebecca E Kreipke ◽

Ondina Palmeira ◽

Connor Dixon ◽

Zachary Goldberg ◽

...

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Stem Cell ◽

Ionizing Radiation ◽

Cell Injury ◽

Germ Line ◽

Adult Stem Cell ◽

Cell Aging ◽

Germline Stem Cells ◽

Cell Cycle Reentry

Aging stem cells lose the capacity to properly respond to injury and regenerate their residing tissues. Here, we utilized the ability of Drosophila melanogaster germline stem cells (GSCs) to survive exposure to low doses of ionizing radiation (IR) as a model of adult stem cell injury and identified a regeneration defect in aging GSCs: while aging GSCs survive exposure to IR, they fail to reenter the cell cycle and regenerate the germline in a timely manner. Mechanistically, we identify foxo and mTOR homologue, Tor as important regulators of GSC quiescence following exposure to ionizing radiation. foxo is required for entry in quiescence, while Tor is essential for cell cycle reentry. Importantly, we further show that the lack of regeneration in aging germ line stem cells after IR can be rescued by loss of foxo.

Download Full-text

Surrogate Measures of Adult Stem Cell Self-Renewal: The Neural Stem Cell Paradigm

Adult Stem Cells ◽

10.1007/978-1-61779-002-7_7 ◽

2011 ◽

pp. 163-179

Author(s):

Loic P. Deleyrolle ◽

Brent A. Reynolds ◽

Florian A. Siebzehnrubl

Keyword(s):

Stem Cell ◽

Neural Stem Cell ◽

Adult Stem Cell ◽

Self Renewal ◽

Surrogate Measures

Download Full-text

A Misexpression Screen Reveals Effects of bag-of-marbles and TGFβ Class Signaling on the Drosophila Male Germ-Line Stem Cell Lineage

Genetics ◽

10.1534/genetics.103.023184 ◽

2004 ◽

Vol 167 (2) ◽

pp. 707-723 ◽

Cited By ~ 120

Author(s):

Cordula Schulz ◽

Amy A. Kiger ◽

Salli I. Tazuke ◽

Yukiko M. Yamashita ◽

Luiz C. Pantalena-Filho ◽

...

Keyword(s):

Stem Cell ◽

Germ Line ◽

Cell Lineage ◽

Male Germ Line ◽

Stem Cell Lineage ◽

Germ Line Stem Cell ◽

Bag Of Marbles

Download Full-text

Progression from a stem cell–like state to early differentiation in the C. elegans germ line

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0912704107 ◽

2010 ◽

Vol 107 (5) ◽

pp. 2048-2053 ◽

Cited By ~ 67

Author(s):

Olivier Cinquin ◽

Sarah L. Crittenden ◽

Dyan E. Morgan ◽

Judith Kimble

Keyword(s):

Stem Cell ◽

Germ Cells ◽

Cell Biology ◽

Germ Line ◽

Stem Cell Biology ◽

Self Renewal ◽

Early Differentiation ◽

C Elegans ◽

Stem Cell Maintenance ◽

System A

Controls of stem cell maintenance and early differentiation are known in several systems. However, the progression from stem cell self-renewal to overt signs of early differentiation is a poorly understood but important problem in stem cell biology. The Caenorhabditis elegans germ line provides a genetically defined model for studying that progression. In this system, a single-celled mesenchymal niche, the distal tip cell (DTC), employs GLP-1/Notch signaling and an RNA regulatory network to balance self-renewal and early differentiation within the “mitotic region,” which continuously self-renews while generating new gametes. Here, we investigate germ cells in the mitotic region for their capacity to differentiate and their state of maturation. Two distinct pools emerge. The “distal pool” is maintained by the DTC in an essentially uniform and immature or “stem cell–like” state; the “proximal pool,” by contrast, contains cells that are maturing toward early differentiation and are likely transit-amplifying cells. A rough estimate of pool sizes is 30–70 germ cells in the distal immature pool and ≈150 in the proximal transit-amplifying pool. We present a simple model for how the network underlying the switch between self-renewal and early differentiation may be acting in these two pools. According to our model, the self-renewal mode of the network maintains the distal pool in an immature state, whereas the transition between self-renewal and early differentiation modes of the network underlies the graded maturation of germ cells in the proximal pool. We discuss implications of this model for controls of stem cells more broadly.

Download Full-text