scholarly journals The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Alexis S Bailey ◽  
Pedro J Batista ◽  
Rebecca S Gold ◽  
Y Grace Chen ◽  
Dirk G de Rooij ◽  
...  
Keyword(s):  
Cell Fate ◽  
Germ Cells ◽  
Meiotic Prophase ◽  
Cell Lineage ◽  
Germline Stem Cell ◽  
Male Germ Cells ◽  
Translational Repressor ◽  
Multiple Transcripts ◽  
Stem Cell Lineage ◽  
Post Transcriptional Regulation

The switch from mitosis to meiosis is the key event marking onset of differentiation in the germline stem cell lineage. In Drosophila, the translational repressor Bgcn is required for spermatogonia to stop mitosis and transition to meiotic prophase and the spermatocyte state. Here we show that the mammalian Bgcn homolog YTHDC2 facilitates a clean switch from mitosis to meiosis in mouse germ cells, revealing a conserved role for YTHDC2 in this critical cell fate transition. YTHDC2-deficient male germ cells enter meiosis but have a mixed identity, maintaining expression of Cyclin A2 and failing to properly express many meiotic markers. Instead of continuing through meiotic prophase, the cells attempt an abnormal mitotic-like division and die. YTHDC2 binds multiple transcripts including Ccna2 and other mitotic transcripts, binds specific piRNA precursors, and interacts with RNA granule components, suggesting that proper progression of germ cells through meiosis is licensed by YTHDC2 through post-transcriptional regulation.

bag-of-marbles and benign gonial cell neoplasm act in the germline to restrict proliferation during Drosophila spermatogenesis

Development ◽  
1997 ◽  
Vol 124 (21) ◽  
pp. 4361-4371 ◽  
Author(s):  
P. Gonczy ◽  
E. Matunis ◽  
S. DiNardo
Keyword(s):  
Stem Cell ◽  
Germ Cells ◽  
Daughter Cell ◽  
Cell Lineage ◽  
Germline Stem Cell ◽  
Cell Lineages ◽  
Male Germline ◽  
Stem Cell Lineage ◽  
Cell Neoplasm ◽  
Bag Of Marbles

Stem cells divide asymmetrically, regenerating a parental stem cell and giving rise to a daughter cell with a distinct fate. In many stem cell lineages, this daughter cell undergoes several amplificatory mitoses, thus generating more cells that embark on the differentiation program specific for the given lineage. Spermatogenesis in Drosophila is a model system to identify molecules regulating stem cell lineages. Mutations at two previously identified loci, bag-of-marbles (bam) and benign gonial cell neoplasm (bgcn), prevent progression through spermatogenesis and oogenesis, resulting in the overproliferation of undifferentiated germ cells. Here we investigate how bam and bgcn regulate the male germline stem cell lineage. By generating FLP-mediated clones, we demonstrate that both bam and bgcn act autonomously in the germline to restrict proliferation during spermatogenesis. By using enhancer trap lines, we find that the overproliferating germ cells express markers specific to amplifying germ cells, while at the same time retaining the expression of some markers of stem cell and primary spermatogonial cell fate. However, we find that germ cells accumulating in bam or bgcn mutant testes most resemble amplifying germ cells, because they undergo incomplete cytokinesis and progress through the cell cycle in synchrony within a cyst, which are two characteristics of amplifying germ cells, but not of stem cells. Taken together, our results suggest that bam and bgcn regulate progression through the male germline stem cell lineage by cell-intrinsically restricting the proliferation of amplifying germ cells.

punt and schnurri regulate a somatically derived signal that restricts proliferation of committed progenitors in the germline

Development ◽  
1997 ◽  
Vol 124 (21) ◽  
pp. 4383-4391 ◽  
Author(s):  
E. Matunis ◽  
J. Tran ◽  
P. Gonczy ◽  
K. Caldwell ◽  
S. DiNardo
Keyword(s):  
Stem Cell ◽  
Germ Cells ◽  
Cell Lineage ◽  
Germline Stem Cell ◽  
Tgf Beta ◽  
Signal Transducers ◽  
Daughter Cells ◽  
Stem Cell Lineage ◽  
Mosaic Analysis ◽  
Cyst Cells

To identify regulators of stem cell lineages, we are focusing on spermatogenesis in Drosophila. In spermatogenesis, each germline stem cell divides asymmetrically, renewing itself and producing a transiently amplifying daughter, which divides four times. By screening for mutants in which daughter cells fail to stop dividing, we find that the TGF-beta signal transducers schnurri and punt are required to limit transient amplification of germ cells. Mosaic analysis demonstrates that punt and schnurri act within somatic cyst cells that surround germ cells, rather than in germ cells. Thus, a cyst-cell-derived signal restricts germ cell proliferation and this signal is initiated by input from a member of the TGF-beta superfamily. Thus, a signal relay regulates progression through the germline stem cell lineage.

scholarly journals Three RNA Binding Proteins Form a Complex to Promote Differentiation of Germline Stem Cell Lineage in Drosophila

PLoS Genetics ◽  
2014 ◽  
Vol 10 (11) ◽  
pp. e1004797 ◽  
Author(s):  
Di Chen ◽  
Chan Wu ◽  
Shaowei Zhao ◽  
Qing Geng ◽  
Yu Gao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Cell Lineage ◽  
Germline Stem Cell ◽  
Stem Cell Lineage

Somatic control over the germline stem cell lineage during Drosophila spermatogenesis

Nature ◽  
2000 ◽  
Vol 407 (6805) ◽  
pp. 754-757 ◽  
Author(s):  
John Tran ◽  
Tamara J. Brenner ◽  
Stephen DiNardo
Keyword(s):  
Stem Cell ◽  
Cell Lineage ◽  
Germline Stem Cell ◽  
Stem Cell Lineage

scholarly journals Twin Promotes the Maintenance and Differentiation of Germline Stem Cell Lineage through Modulation of Multiple Pathways

Cell Reports ◽  
2015 ◽  
Vol 13 (7) ◽  
pp. 1366-1379 ◽  
Author(s):  
Ziwen Fu ◽  
Cuiyun Geng ◽  
Hui Wang ◽  
Zhihao Yang ◽  
Changjiang Weng ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lineage ◽  
Germline Stem Cell ◽  
Stem Cell Lineage

scholarly journals Biomimetic three-dimensional microenvironment for controlling stem cell fate

2011 ◽  
Vol 1 (5) ◽  
pp. 792-803 ◽  
Author(s):  
Hu Zhang ◽  
Sheng Dai ◽  
Jingxiu Bi ◽  
Kuo-Kang Liu
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Three Dimensional ◽  
Cell Lineage ◽  
Cell Interaction ◽  
Stem Cell Fate ◽  
Cell Microenvironment ◽  
Stem Cell Lineage ◽  
Matrix Cell ◽  
The Individual

Stem cell therapy is an emerging technique which is being translated into treatment of degenerated tissues. However, the success of translation relies on the stem cell lineage commitment in the degenerated regions of interest. This commitment is precisely controlled by the stem cell microenvironment. Engineering a biomimetic three-dimensional microenvironment enables a thorough understanding of the mechanisms of governing stem cell fate. We review the individual microenvironment components, including soluble factors, extracellular matrix, cell–cell interaction and mechanical stimulation. The perspectives in creating the biomimetic microenvironments are discussed with emerging techniques.

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