scholarly journals Ectopic POU5F1 in the male germ lineage disrupts differentiation and spermatogenesis in mice

Reproduction ◽  
2016 ◽  
Vol 152 (4) ◽  
pp. 363-377 ◽  
Author(s):  
Yu Zheng ◽  
LeAnna J Phillips ◽  
Rachel Hartman ◽  
Junhui An ◽  
Christina T Dann
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Germ Cells ◽  
Progenitor Cell ◽  
Ectopic Expression ◽  
Transgenic Mouse Model ◽  
Spermatogonial Stem Cell ◽  
Early Embryogenesis ◽  
Cell Lineages ◽  
Progenitor Cell Population

Expression levels of the pluripotency determinant, POU5F1, are tightly regulated to ensure appropriate differentiation during early embryogenesis. POU5F1 is also present in the spermatogonial stem cell/progenitor cell population in mice and it is downregulated as spermatogenesis progresses. To test if POU5F1 downregulation is required for SSCs to differentiate, we produced transgenic mice that ubiquitously express POU5F1 in Cre-expressing lineages. Using a Vasa-Cre driver to produce ectopic POU5F1 in all postnatal germ cells, we found that POU5F1 downregulation was necessary for spermatogonial expansion during the first wave of spermatogenesis and for the production of differentiated spermatogonia capable of undergoing meiosis. In contrast, undifferentiated spermatogonia were maintained throughout adulthood, consistent with a normal presence of POU5F1 in these cells. The results suggest that POU5F1 downregulation in differentiating spermatogonia is a necessary step for the progression of spermatogenesis. Further, the creation of a transgenic mouse model for conditional ectopic expression of POU5F1 may be a useful resource for studies of POU5F1 in other cell lineages, during tumorogenesis and cell fate reprogramming.

Ectopic expression of the Drosophila Bam protein eliminates oogenic germline stem cells

Development ◽  
1997 ◽  
Vol 124 (18) ◽  
pp. 3651-3662 ◽  
Author(s):  
B. Ohlstein ◽  
D. McKearin
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Germ Cell ◽  
Cell Fate ◽  
Germ Cells ◽  
Ectopic Expression ◽  
Cell Lineage ◽  
Limiting Factor ◽  
Germline Stem Cells ◽  
Stem Cell Divisions

The Drosophila germ-cell lineage has emerged as a remarkable system for identifying genes required for changes in cell fate from stem cells into more specialized cells. Previous work indicates that bam expression is necessary for cystoblast differentiation; bam mutant germ cells fail to differentiate, but instead proliferate like stem cells. This paper reports that ectopic expression of bam is sufficient to extinguish stem cell divisions. Heat-induced bam+ expression specifically eliminated oogenic stem cells while somatic stem cell populations were not affected. Together with previous studies of the timing of bam mRNA and protein expression and the state of arrest in bam mutant cells, these data implicate Bam as a direct regulator of the switch from stem cell to cystoblast. Surprisingly, ectopic bam+ had no deleterious consequences for male germline cells suggesting that Bam may regulate somewhat different steps of germ-cell development in oogenesis and spermatogenesis. We discuss a model for how bam+ could direct differentiation based on our data (McKearin and Ohlstein, 1995) that Bam protein is essential to assemble part of the germ-cell-specific organelle, the fusome. We propose that fusome biogenesis is an obligate step for cystoblast cell fate and that Bam is the limiting factor for fusome maturation in female germ cells.

scholarly journals The WT1-like transcription factor Klumpfuss maintains lineage commitment of enterocyte progenitors in the Drosophila intestine

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jerome Korzelius ◽  
Sina Azami ◽  
Tal Ronnen-Oron ◽  
Philipp Koch ◽  
Maik Baldauf ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Differentiation ◽  
Cell Fate ◽  
Progenitor Cell ◽  
Lineage Commitment ◽  
Proneural Gene ◽  
Cell Lineages ◽  
Daughter Cells ◽  
Mechanistic Insight ◽  
Insight Into

Abstract In adult epithelial stem cell lineages, the precise differentiation of daughter cells is critical to maintain tissue homeostasis. Notch signaling controls the choice between absorptive and entero-endocrine cell differentiation in both the mammalian small intestine and the Drosophila midgut, yet how Notch promotes lineage restriction remains unclear. Here, we describe a role for the transcription factor Klumpfuss (Klu) in restricting the fate of enteroblasts (EBs) in the Drosophila intestine. Klu is induced in Notch-positive EBs and its activity restricts cell fate towards the enterocyte (EC) lineage. Transcriptomics and DamID profiling show that Klu suppresses enteroendocrine (EE) fate by repressing the action of the proneural gene Scute, which is essential for EE differentiation. Loss of Klu results in differentiation of EBs into EE cells. Our findings provide mechanistic insight into how lineage commitment in progenitor cell differentiation can be ensured downstream of initial specification cues.

scholarly journals Mechanisms of Stem Cell Factor and Erythropoietin Proliferative Co-signaling in FDC2-ER Cells

Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3533-3545 ◽  
Author(s):  
Bhavana Joneja ◽  
Hong-Chi Chen ◽  
Dhaya Seshasayee ◽  
Amy L. Wrentmore ◽  
Don M. Wojchowski
Keyword(s):  
Stem Cell ◽  
Cell Lines ◽  
Stem Cell Factor ◽  
Progenitor Cell ◽  
Egf Receptor ◽  
Synergistic Effects ◽  
Ectopic Expression ◽  
Hematopoietic Progenitor Cell ◽  
Detectable Effect ◽  
Epo Receptor

Abstract Studies of hematopoietic progenitor cell development in vivo, ex vivo, and in factor-dependent cell lines have shown that c-kit promotes proliferation through synergistic effects with at least certain type 1 cytokine receptors, including the erythropoietin (Epo) receptor. Presently, c-kit is shown to efficiently support both mitogenesis and survival in the FDCP1 cell subline, FDC2. In this system, mitogenic synergy with c-kit was observed for ectopically expressed wild-type Epo receptors (wt-ER), an epidermal growth factor (EGF) receptor/Epo receptor chimera, and a highly truncated Epo receptor construct ER-Bx1. Thus, the Epo receptor cytoplasmic box 1 subdomain appears, at least in part, to mediate mitogenic synergy with c-kit. In studies of potential effectors of this response, Jak2 tyrosine phosphorylation was shown to be induced by Epo, but not by stem cell factor (SCF). In addition and in contrast to signaling in Mo7e and BM6 cell lines, in FDC2-ER cells SCF and Epo each were shown to rapidly activate Pim 1 gene expression. Recently, roles also have been suggested for the nuclear trans-factor GATA-1 in regulating progenitor cell proliferation. In FDC2-ER cells, the ectopic expression of GATA-1 had no detectable effect on Epo inhibition of apoptosis. However, GATA-1 expression did result in a selective and marked inhibition in mitogenic responsiveness to SCF and to a decrease in c-kit transcript expression. These studies of SCF and Epo signaling in FDC2–wt-ER cells serve to functionally map the ERB1 region as a c-kit–interactive domain, suggest that Pim1 might contribute to SCF and Epo mitogenic synergy and support the notion that SCF and Epo may act in opposing ways during red cell differentiation.

335 Divergent VEGFA signaling determines spermatogonial stem cell fate

2016 ◽  
Vol 94 (suppl_2) ◽  
pp. 157-158
Author(s):  
K. M. Sargent ◽  
J. R. Essink ◽  
M. L. Bremer ◽  
W. E. Pohlmeier ◽  
M. M. Laughlin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Spermatogonial Stem Cell ◽  
Stem Cell Fate

scholarly journals Reconstruction of rat retinal progenitor cell lineages in vitro reveals a surprising degree of stochasticity in cell fate decisions

Development ◽  
2010 ◽  
Vol 138 (2) ◽  
pp. 227-235 ◽  
Author(s):  
F. L. A. F. Gomes ◽  
G. Zhang ◽  
F. Carbonell ◽  
J. A. Correa ◽  
W. A. Harris ◽  
...  
Keyword(s):  
Cell Fate ◽  
Progenitor Cell ◽  
Retinal Progenitor Cell ◽  
Cell Fate Decisions ◽  
Cell Lineages ◽  
Retinal Progenitor

scholarly journals m6A is required for resolving progenitor identity during planarian stem cell differentiation

2021 ◽  
Author(s):  
Yael Dagan ◽  
Yarden Yesharim ◽  
Ashley R. Bonneau ◽  
Schraga Schwartz ◽  
Peter W. Reddien ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Cell Fate ◽  
Stem Cell Differentiation ◽  
Histone Variants ◽  
Cell Lineages ◽  
Base Modification ◽  
Undifferentiated Cells ◽  
Chromatin Modifying Complex ◽  
Transcriptional State

Regeneration requires accurate production of missing cell lineages. Cell production is driven by changes to gene expression, which is shaped by multiple layers of regulation. Here, we find that the ubiquitous mRNA base-modification, m6A, is required for proper cell fate choice and cellular maturation in planarian stem cells (neoblasts). We mapped m6A-enriched regions in 7,600 planarian genes, and found that perturbation of the m6A pathway resulted in progressive deterioration of tissues and death. Using single cell RNA sequencing of >20,000 cells following perturbation of the pathway, we discovered that m6A negatively regulates transcription of histone variants, and that inhibition of the pathway resulted in accumulation of undifferentiated cells throughout the animal in an abnormal transcriptional state. Analysis of >1000 planarian gene expression datasets revealed that the inhibition of the chromatin modifying complex NuRD had almost indistinguishable consequences, unraveling an unappreciated link between m6A and chromatin modifications. Our findings reveal that m6A is critical for planarian stem cell homeostasis and gene regulation in regeneration.

STK31 acts as a cell fate determinant in spermatogonial stem cell

2010 ◽  
Vol 34 (8) ◽  
pp. S37-S37
Author(s):  
Kin Lam Ellis Fok ◽  
Chin Man Chung ◽  
Hsiao Chang Chan
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Spermatogonial Stem Cell ◽  
Cell Fate Determinant ◽  
A Cell

scholarly journals Regulating the regulator: Numb acts upstream of p53 to control mammary stem and progenitor cell

2015 ◽  
Vol 211 (4) ◽  
pp. 737-739 ◽  
Author(s):  
Marisa M. Faraldo ◽  
Marina A. Glukhova
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Expansion ◽  
Progenitor Cell ◽  
Asymmetric Cell Divisions ◽  
Stem Cell Expansion ◽  
Cell Divisions ◽  
Cell Fate Determinant ◽  
Mammary Stem

In this issue, Tosoni et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201505037) report that cell fate determinant and tumor suppressor Numb imposes asymmetric cell divisions in mammary stem cells by regulating p53. Numb thereby restricts mammary stem cell expansion and controls the proliferation and lineage-specific characteristics of their progeny.

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