scholarly journals Identification of slow-cycling germline stem cells and their regulation by PLZF

2018 ◽  
Author(s):  
Manju Sharma ◽  
Anuj Srivastava ◽  
Heather E. Fairfield ◽  
David Bergstrom ◽  
William F. Flynn ◽  
...  
Keyword(s):  
Lineage Tracing ◽  
Proliferation Index ◽  
Germline Stem Cells ◽  
Wild Type ◽  
T Box ◽  
Slow Cycling ◽  
Essential Growth ◽  
Essential Growth Factor ◽  
Term Maintenance

ABSTRACTLong-term maintenance of spermatogenesis in mammals is supported by GDNF, an essential growth factor required for spermatogonial stem cell (SSC) self-renewal. Exploiting a transgenic GDNF overexpression model, which expands and normalizes the pool of undifferentiated spermatogonia between Plzf+/+ and Plzflu/lu mice, we used RNAseq to identify a rare subpopulation of cells that express EOMES, a T-box transcription factor. Lineage tracing and busulfan challenge show that these are long-term SSCs that contribute to steady state spermatogenesis as well as regeneration following chemical injury. EOMES+ SSCs have a lower proliferation index than EOMES− GFRA1+ spermatogonia in wild-type but not in Plzflu/lu mice. This comparison demonstrates that PLZF regulates their proliferative activity and suggests that EOMES+ SSCs are lost through proliferative exhaustion in Plzflu/lu mice. Single cell RNA sequencing of EOMES+ cells from Plzf+/+ and Plzflu/lu mice support a hierarchical model of both slow- and rapid-cycling SSCs.

scholarly journals Identification of EOMES-expressing spermatogonial stem cells and their regulation by PLZF

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Manju Sharma ◽  
Anuj Srivastava ◽  
Heather E Fairfield ◽  
David Bergstrom ◽  
William F Flynn ◽  
...  
Keyword(s):  
Spermatogonial Stem Cell ◽  
Lineage Tracing ◽  
Proliferation Index ◽  
Wild Type ◽  
Self Renewal ◽  
T Box ◽  
Essential Growth ◽  
Essential Growth Factor ◽  
Term Maintenance

Long-term maintenance of spermatogenesis in mammals is supported by GDNF, an essential growth factor required for spermatogonial stem cell (SSC) self-renewal. Exploiting a transgenic GDNF overexpression model, which expands and normalizes the pool of undifferentiated spermatogonia between Plzf +/+ and Plzf lu/lu mice, we used RNAseq to identify a rare subpopulation of cells that express EOMES, a T-box transcription factor. Lineage tracing and busulfan challenge show that these are SSCs that contribute to steady state spermatogenesis as well as regeneration following chemical injury. EOMES+ SSCs have a lower proliferation index in wild-type than in Plzf lu/lu mice, suggesting that PLZF regulates their proliferative activity and that EOMES+ SSCs are lost through proliferative exhaustion in Plzf lu/lu mice. Single cell RNA sequencing of EOMES+ cells from Plzf +/+ and Plzf lu/lu mice support the conclusion that SSCs are hierarchical yet heterogeneous.

scholarly journals Heterogeneity of murine periosteum progenitors involved in fracture healing

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Brya G Matthews ◽  
Sanja Novak ◽  
Francesca V Sbrana ◽  
Jessica L Funnell ◽  
Ye Cao ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Progenitor Cells ◽  
Smooth Muscle Actin ◽  
Lineage Tracing ◽  
Bone Fracture Healing ◽  
Alpha Smooth Muscle Actin ◽  
Colony Forming Units ◽  
Slow Cycling ◽  
Stem Cell Populations

The periosteum is the major source of cells involved in fracture healing. We sought to characterize progenitor cells and their contribution to bone fracture healing. The periosteum is highly enriched with progenitor cells, including Sca1+ cells, fibroblast colony-forming units, and label-retaining cells compared to the endosteum and bone marrow. Using lineage tracing, we demonstrate that alpha smooth muscle actin (αSMA) identifies long-term, slow-cycling, self-renewing osteochondroprogenitors in the adult periosteum that are functionally important for bone formation during fracture healing. In addition, Col2.3CreER-labeled osteoblast cells contribute around 10% of osteoblasts but no chondrocytes in fracture calluses. Most periosteal osteochondroprogenitors following fracture can be targeted by αSMACreER. Previously identified skeletal stem cell populations were common in periosteum but contained high proportions of mature osteoblasts. We have demonstrated that the periosteum is highly enriched with skeletal progenitor cells, and there is heterogeneity in the populations of cells that contribute to mature lineages during periosteal fracture healing.

scholarly journals Lineage hierarchies and stochasticity ensure the long-term maintenance of adult neural stem cells

2020 ◽  
Vol 6 (18) ◽  
pp. eaaz5424 ◽  
Author(s):  
Emmanuel Than-Trong ◽  
Bahareh Kiani ◽  
Nicolas Dray ◽  
Sara Ortica ◽  
Benjamin Simons ◽  
...  
Keyword(s):  
Lineage Tracing ◽  
Hierarchical Organization ◽  
Genetic Lineage ◽  
Self Renewal ◽  
Functional Behavior ◽  
Asymmetric Divisions ◽  
Genetic Lineage Tracing ◽  
Global Population ◽  
Term Maintenance

The cellular basis and extent of neural stem cell (NSC) self-renewal in adult vertebrates, and their heterogeneity, remain controversial. To explore the functional behavior and dynamics of individual NSCs, we combined genetic lineage tracing, quantitative clonal analysis, intravital imaging, and global population assessments in the adult zebrafish telencephalon. Our results are compatible with a model where adult neurogenesis is organized in a hierarchy in which a subpopulation of deeply quiescent reservoir NSCs with long-term self-renewal potential generate, through asymmetric divisions, a pool of operational NSCs activating more frequently and taking stochastic fates biased toward neuronal differentiation. Our data further suggest the existence of an additional, upstream, progenitor population that supports the continuous generation of new reservoir NSCs, thus contributing to their overall expansion. Hence, we propose that the dynamics of vertebrate neurogenesis relies on a hierarchical organization where growth, self-renewal, and neurogenic functions are segregated between different NSC types.

scholarly journals Phosphorus status of diverse soils in Finland as influenced by long-term P fertilisation 2.Changes of soil test values in relation to P balance with references to incorporation depth of residual and freshly applied P

2008 ◽  
Vol 13 (3) ◽  
pp. 276 ◽  
Author(s):  
I. SAARELA ◽  
A. JÄRVI ◽  
H. HAKKOLA
Keyword(s):  
Field Experiments ◽  
Soil Test ◽  
Broadcast Application ◽  
Subsurface Soil ◽  
Soil Test P ◽  
P Balance ◽  
P Application ◽  
Essential Growth ◽  
Essential Growth Factor

Fertilising with phosphorus (P) ensures continuous supply of an essential growth factor as necessary for productive and sustainable agriculture. The amounts of P required to attain and maintain an adequate P status in the soil were investigated in field experiments at 22 sites in Finland on soils containing large amounts of residual fertiliser P. The effects of five rates (0, 15, 30, 45 and 60 kg ha-1) of annual P application were measured in the soil by chemical methods after 9 to 15 experimental years, and the changes in soil test P values (STP) were compared with P balances. Stratification of P in ley soil by broadcast application of fertilisers was assessed at four sites. The mean changes of STP in the whole topsoil caused by P fertilisation expressed as per cent of the balance difference were 3.5% (0.0159 mg dm-3)/(kg ha-1) in the acid ammonium acetate test (PAc), 4.7% (0.0214 mg dm-3)/(kg ha-1) in water extraction (Pw) and 9.7% (0.058 mg kg-1)/(kg ha-1) in sodium bicarbonate extraction (modified Olsen P). Initially high PAc values tended to slowly decrease at zero P balance, while low values did not change without some particular reason, such as soil acidification or mixing of the topsoil with some of the less fertile subsurface soil. A thin layer of the uppermost soil was quickly enriched by broadcast application of P fertiliser.;

scholarly journals Oligodendrocytes support axonal transport and maintenance via exosome secretion

PLoS Biology ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. e3000621
Author(s):  
Carsten Frühbeis ◽  
Wen Ping Kuo-Elsner ◽  
Christina Müller ◽  
Kerstin Barth ◽  
Leticia Peris ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Axonal Degeneration ◽  
Specific Gene ◽  
Wild Type ◽  
Neuronal Viability ◽  
Mouse Mutants ◽  
Gene Defects ◽  
Term Maintenance

Neurons extend long axons that require maintenance and are susceptible to degeneration. Long-term integrity of axons depends on intrinsic mechanisms including axonal transport and extrinsic support from adjacent glial cells. The mechanisms of support provided by myelinating oligodendrocytes to underlying axons are only partly understood. Oligodendrocytes release extracellular vesicles (EVs) with properties of exosomes, which upon delivery to neurons improve neuronal viability in vitro. Here, we show that oligodendroglial exosome secretion is impaired in 2 mouse mutants exhibiting secondary axonal degeneration due to oligodendrocyte-specific gene defects. Wild-type oligodendroglial exosomes support neurons by improving the metabolic state and promoting axonal transport in nutrient-deprived neurons. Mutant oligodendrocytes release fewer exosomes, which share a common signature of underrepresented proteins. Notably, mutant exosomes lack the ability to support nutrient-deprived neurons and to promote axonal transport. Together, these findings indicate that glia-to-neuron exosome transfer promotes neuronal long-term maintenance by facilitating axonal transport, providing a novel mechanistic link between myelin diseases and secondary loss of axonal integrity.

scholarly journals Lineage hierarchies and stochasticity ensure the long-term maintenance of adult neural stem cells

2019 ◽  
Author(s):  
Emmanuel Than-Trong ◽  
Bahareh Kiani ◽  
Nicolas Dray ◽  
Sara Ortica ◽  
Benjamin Simons ◽  
...  
Keyword(s):  
Lineage Tracing ◽  
Hierarchical Organization ◽  
Genetic Lineage ◽  
Self Renewal ◽  
Functional Behavior ◽  
Genetic Lineage Tracing ◽  
Global Population ◽  
Term Maintenance ◽  
New Reservoir

AbstractThe cellular basis and extent of neural stem cell (NSC) self-renewal in adult vertebrates, and their heterogeneity, remain controversial. To explore the functional behavior and dynamics of individual NSCs within brain germinal pools, we combined genetic lineage tracing, quantitative clonal analysis, intravital imaging and global population assessments in the adult zebrafish telencephalon. We show that adult neurogenesis is organized in a hierarchy where a subpopulation of reservoir NSCs with longterm self-renewal potential generate a pool of operational NSCs taking stochastic fates biased towards neuronal differentiation. To fuel the long-term growth of the adult germinal niche, we provide evidence for the existence of an additional, upstream, progenitor population that supports the continuous generation of new reservoir NSCs, contributing to their overall expansion. Hence, the dynamics of vertebrate neurogenesis relies on a hierarchical organization where growth, self-renewal and neurogenic functions are segregated between different NSC types.

Efficacious long-term maintenance therapy with pantoprazole (PAN) in patients with Zollinger-Ellison syndrome

2001 ◽  
Vol 120 (5) ◽  
pp. A613-A613
Author(s):  
P BORNMAN ◽  
K RADEBOLD ◽  
H DEBAERE ◽  
L VENTER ◽  
H HEINZE ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Zollinger Ellison Syndrome ◽  
Term Maintenance
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