Drosophila YBX1 homolog YPS promotes ovarian germ line stem cell development by preferentially recognizing 5-methylcytosine RNAs

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

Faculty Opinions recommendation of MILI, a PIWI-interacting RNA-binding protein, is required for germ line stem cell self-renewal and appears to positively regulate translation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1157685.617895 ◽

2009 ◽

Author(s):

Nicola Gray ◽

Matt Brook

Keyword(s):

Stem Cell ◽

Rna Binding ◽

Germ Line ◽

Binding Protein ◽

Rna Binding Protein ◽

Self Renewal ◽

Germ Line Stem Cell

Download Full-text

Dynamic Mechanical Properties Control Adult Stem Cell Fate

ASME 2012 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2012-80062 ◽

2012 ◽

Author(s):

Murat Guvendiren ◽

Jason A. Burdick

Keyword(s):

Stem Cell ◽

Cell Fate ◽

Adult Stem Cell ◽

Dynamic Mechanical Properties ◽

Cellular Functions ◽

Cellular Processes ◽

Proliferation And Differentiation ◽

Important Field ◽

Control Adult

Stem cells respond to many microenvironmental cues towards their decisions to spread, migrate, and differentiate and these cues can be incorporated into materials for regenerative medicine.1 In the last decade, matrix stiffness alone has been implicated in regulating cellular functions such as migration, proliferation and differentiation. With this in mind, a variety of natural and synthetic polymer systems were used in vitro to mimic the elasticity of native tissues. Despite helping to develop this important field and gather valuable information, these substrates are primarily static and lack the dynamic nature that is observed during many cellular processes such as development, fibrosis and cancer. Thus, it is of great interest to temporally manipulate matrix elasticity in vitro to better understand and develop strategies to control these biological processes. In this work, we utilize a sequential crosslinking approach (initial gelation via addition reaction, secondary crosslinking through light-mediated radical polymerization) to fabricate hydrogel substrates that stiffen (e.g., ∼3 to 30 kPa) either immediately or at later times and in the presence of cells. We demonstrate the utility of this technique by investigating the short-term (several minutes to hours) and long-term (several days to weeks) stem cell response to dynamic stiffening

Download Full-text

In Vitro Cytotoxicity of Nanoparticles in Mammalian Germ-Line Stem Cell

Toxicological Sciences ◽

10.1093/toxsci/kfi340 ◽

2005 ◽

Vol 88 (2) ◽

pp. 285-286 ◽

Cited By ~ 13

Author(s):

Maria Pilar Vinardell

Keyword(s):

Stem Cell ◽

Germ Line ◽

In Vitro Cytotoxicity ◽

Germ Line Stem Cell

Download Full-text

Essential requirement of mammalian Pumilio family in embryonic development

Molecular Biology of the Cell ◽

10.1091/mbc.e18-06-0369 ◽

2018 ◽

Vol 29 (24) ◽

pp. 2922-2932 ◽

Cited By ~ 8

Author(s):

Kaibo Lin ◽

Shikun Zhang ◽

Qinghua Shi ◽

Mengyi Zhu ◽

Liuze Gao ◽

...

Keyword(s):

Stem Cell ◽

Embryonic Development ◽

Rna Binding ◽

Germ Line ◽

Embryonic Stem ◽

Cell Development ◽

Luciferase Reporter ◽

Essential Requirement ◽

Stem Cell Maintenance ◽

Cell Maintenance

Mouse PUMILIO1 (PUM1) and PUMILIO2 (PUM2) belong to the PUF (Pumilio/FBF) family, a highly conserved RNA binding protein family whose homologues play critical roles in embryonic development and germ line stem cell maintenance in invertebrates. However, their roles in mammalian embryonic development and stem cell maintenance remained largely uncharacterized. Here we report an essential requirement of the Pum gene family in early embryonic development. A loss of both Pum1 and Pum2 genes led to gastrulation failure, resulting in embryo lethality at E8.5. Pum-deficient blastocysts, however, appeared morphologically normal, from which embryonic stem cells (ESCs) could be established. Both mutant ESCs and embryos exhibited reduced growth and increased expression of endoderm markers Gata6 and Lama1, making defects in growth and differentiation the likely causes of gastrulation failure. Furthermore, ESC Gata6 transcripts could be pulled down via PUM1 immunoprecipitation and mutation of conserved PUM-binding element on 3′UTR (untranslated region) of Gata6 enhanced the expression of luciferase reporter, implicating PUM-mediated posttranscriptional regulation of Gata6 expression in stem cell development and cell lineage determination. Hence, like its invertebrate homologues, mouse PUM proteins are conserved posttranscriptional regulators essential for embryonic and stem cell development.

Download Full-text