scholarly journals The follicle epithelium in the Drosophila ovary is maintained by a small number of stem cells

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Jocelyne Fadiga ◽  
Todd G Nystul
Keyword(s):  
Stem Cells ◽  
Cell Biology ◽  
Clonal Analysis ◽  
Follicle Cells ◽  
Stem Cell Biology ◽  
Research Support ◽  
Clone Size ◽  
New Methods ◽  
Follicle Stem Cells ◽  
Drosophila Ovary

The follicle stem cells (FSCs) in the Drosophila ovary are an important experimental model for the study of epithelial stem cell biology. Although decades of research support the conclusion that there are two FSCs per ovariole, a recent study used a novel clonal marking system to conclude that there are 15–16 FSCs per ovariole. We performed clonal analysis using both this novel clonal marking system and standard clonal marking systems, and identified several problems that may have contributed to the overestimate of FSC number. In addition, we developed new methods for accurately measuring clone size, and found that FSC clones produce, on average, half of the follicle cells in each ovariole. Our findings provide strong independent support for the conclusion that there are typically two active FSCs per ovariole, though they are consistent with up to four FSCs per germarium.

scholarly journals Adult stem cells and niche cells segregate gradually from common precursors that build the adult Drosophila ovary during pupal development

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Amy Reilein ◽  
Helen V Kogan ◽  
Rachel Misner ◽  
Karen Sophia Park ◽  
Daniel Kalderon
Keyword(s):  
Stem Cells ◽  
Adult Stem Cells ◽  
Spatial Organization ◽  
Follicle Cells ◽  
Pupal Development ◽  
Adult Cell ◽  
Germline Cyst ◽  
Follicle Stem Cells ◽  
Drosophila Ovary ◽  
Adult Drosophila

Production of proliferative Follicle Cells (FCs) and quiescent Escort Cells (ECs) by Follicle Stem Cells (FSCs) in adult Drosophila ovaries is regulated by niche signals from anterior (Cap Cells, ECs) and posterior (polar FCs) sources. Here we show that ECs, FSCs and FCs develop from common pupal precursors, with different fates acquired by progressive separation of cells along the AP axis and a graded decline in anterior cell proliferation. ECs, FSCs and most FCs derive from Intermingled Cell (IC) precursors interspersed with germline cells. Precursors also accumulate posterior to ICs before engulfing a naked germline cyst projected out of the germarium to form the first egg chamber and posterior polar FC signaling center. Thus, stem and niche cells develop in appropriate numbers and spatial organization through regulated proliferative expansion together with progressive establishment of spatial signaling cues that guide adult cell behavior, rather than through rigid early specification events.

Establishment of human OCT4 as a putative HSP90 client protein : a case for HSP90 chaperoning pluripotency

2015 ◽  
Author(s):  
◽  
Jason Neville Sterrenberg
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Stem Cell ◽  
Cell Biology ◽  
Therapeutic Potential ◽  
Stem Cell Biology ◽  
Client Protein ◽  
Hsp90 Inhibition ◽  
Regulated Gene Expression ◽  
Hsp90 Client Protein

The therapeutic potential of stem cells is already being harnessed in clinical trails. Of even greater therapeutic potential has been the discovery of mechanisms to reprogram differentiated cells into a pluripotent stem cell-like state known as induced pluripotent stem cells (iPSCs). Stem cell nature is governed and maintained by a hierarchy of transcription factors, the apex of which is OCT4. Although much research has elucidated the transcriptional regulation of OCT4, OCT4 regulated gene expression profiles and OCT4 transcriptional activation mechanisms in both stem cell biology and cellular reprogramming to iPSCs, the fundamental biochemistry surrounding the OCT4 transcription factor remains largely unknown. In order to analyze the biochemical relationship between HSP90 and human OCT4 we developed an exogenous active human OCT4 expression model with human OCT4 under transcriptional control of a constitutive promoter. We identified the direct interaction between HSP90 and human OCT4 despite the fact that the proteins predominantly display differential subcellular localizations. We show that HSP90 inhibition resulted in degradation of human OCT4 via the ubiquitin proteasome degradation pathway. As human OCT4 and HSP90 did not interact in the nucleus, we suggest that HSP90 functions in the cytoplasmic stabilization of human OCT4. Our analysis suggests HSP90 inhibition inhibits the transcriptional activity of human OCT4 dimers without affecting monomeric OCT4 activity. Additionally our data suggests that the HSP90 and human OCT4 complex is modulated by phosphorylation events either promoting or abrogating the interaction between HSP90 and human OCT4. Our data suggest that human OCT4 displays the characteristics describing HSP90 client proteins, therefore we identify human OCT4 as a putative HSP90 client protein. The regulation of the transcription factor OCT4 by HSP90 provides fundamental insights into the complex biochemistry of stem cell biology. This may also be suggestive that HSP90 not only regulates stem cell biology by maintaining routine cellular homeostasis but additionally through the direct regulation of pluripotency factors.

3. Personalized pluripotent stem cells

2021 ◽  
pp. 39-51
Author(s):  
Jonathan Slack
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cell Biology ◽  
Nuclear Transplantation ◽  
Stem Cell Biology ◽  
Normal Cells ◽  
Specific Patient ◽  
No Formation ◽  
Induced Pluripotent ◽  
The Individual

‘Personalized pluripotent stem cells’ discusses cloning and its connection to stem cell biology. Somatic cell nuclear transplantation into oocytes can make personalized pluripotent stem cells as a perfect genetic match to a specific patient that provoke no immune rejection on grafting. Because this procedure involves generation of cells but no formation of an actual cloned individual, it has become known as human therapeutic cloning. Induced pluripotent stem cells (iPS cells) are made by introducing a few specific genes into normal cells. They are also a perfect genetic match to the individual donating the normal cells and because they are easy to make are now the preferred source.

scholarly journals Toward Personalized Cell Therapies by Using Stem Cells: Seven Relevant Topics for Safety and Success in Stem Cell Therapy

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Fernando de Sá Silva ◽  
Paula Nascimento Almeida ◽  
João Vitor Paes Rettore ◽  
Claudinéia Pereira Maranduba ◽  
Camila Maurmann de Souza ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Cell Biology ◽  
Stem Cell Biology ◽  
Controversial Issues ◽  
Immunosuppressive Activity ◽  
Cell Therapies ◽  
Tumorigenic Potential ◽  
Wide Range

Stem cells, both embryonic and adult, due to the potential for application in tissue regeneration have been the target of interest to the world scientific community. In fact, stem cells can be considered revolutionary in the field of medicine, especially in the treatment of a wide range of human diseases. However, caution is needed in the clinical application of such cells and this is an issue that demands more studies. This paper will discuss some controversial issues of importance for achieving cell therapy safety and success. Particularly, the following aspects of stem cell biology will be presented: methods for stem cells culture, teratogenic or tumorigenic potential, cellular dose, proliferation, senescence, karyotyping, and immunosuppressive activity.

scholarly journals A pluri- és multipotencia határán: a ganglionléc őssejtjei

2015 ◽  
Vol 156 (42) ◽  
pp. 1683-1694
Author(s):  
Gyöngyi Kudlik ◽  
Zsolt Matula ◽  
Tamás Kovács ◽  
S. Veronika Urbán ◽  
Ferenc Uher
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Neural Crest ◽  
Cell Biology ◽  
Pigment Cells ◽  
Stem Cell Biology ◽  
Vertebrate Embryos ◽  
Derivatives Of ◽  
Review Current ◽  
Migratory Cell

The neural crest is a transient, multipotent, migratory cell population that is unique to vertebrate embryos and gives rise to many derivatives, ranging from the neuronal and glial components of the peripheral nervous system to the ectomesenchymal derivatives of the craniofacial area and pigment cells in the skin. Intriguingly, the neural crest derived stem cells are not only present in the embryonic neural crest, but also in their target tissues in the fetus and adult. These postmigratory stem cells, at least partially, resemble their multipotency. Moreover, fully differentiated neural crest-derived cells such as Schwann cells and melanocytes are able to dedifferentiate into stem-like progenitors. Here the authors review current understanding of this unique plasticity and its potential application in stem cell biology as well as in regenerative medicine. Orv. Hetil., 2015, 156(42), 1683–1694.

Realistic Prospects for Stem Cell Therapeutics

Hematology ◽  
2003 ◽  
Vol 2003 (1) ◽  
pp. 398-418 ◽  
Author(s):  
George Q. Daley ◽  
Margaret A. Goodell ◽  
Evan Y. Snyder
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Cell Biology ◽  
Adult Stem Cells ◽  
Stem Cell Biology ◽  
Cell Therapies ◽  
The Media ◽  
New Treatment ◽  
Definition Of

Abstract Studies of the regenerating hematopoietic system have led to the definition of many of the fundamental principles of stem cell biology. Therapies based on a range of tissue stem cells have been widely touted as a new treatment modality, presaging an emerging new specialty called regenerative medicine that promises to harness stem cells from embryonic and somatic sources to provide replacement cell therapies for genetic, malignant, and degenerative conditions. Insights borne from stem cell biology also portend development of protein and small molecule therapeutics that act on endogenous stem cells to promote repair and regeneration. Much of the newfound enthusiasm for regenerative medicine stems from the hope that advances in the laboratory will be followed soon thereafter by breakthrough treatments in the clinic. But how does one sort through the hype to judge the true promise? Are stem cell biologists and the media building expectations that cannot be met? Which diseases can be treated, and when can we expect success? In this review, we outline the realms of investigation that are capturing the most attention, and consider the current state of scientific understanding and controversy regarding the properties of embryonic and somatic (adult) stem cells. Our objective is to provide a framework for appreciating the promise while at the same time understanding the challenges behind translating fundamental stem cell biology into novel clinical therapies.

scholarly journals Extracellular Vesicles: Evolving Factors in Stem Cell Biology

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Muhammad Nawaz ◽  
Farah Fatima ◽  
Krishna C. Vallabhaneni ◽  
Patrice Penfornis ◽  
Hadi Valadi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tumor Microenvironment ◽  
Extracellular Vesicles ◽  
Cell Biology ◽  
Trophic Factors ◽  
Stem Cell Biology ◽  
Cell Fates ◽  
Bidirectional Communication

Stem cells are proposed to continuously secrete trophic factors that potentially serve as mediators of autocrine and paracrine activities, associated with reprogramming of the tumor microenvironment, tissue regeneration, and repair. Hitherto, significant efforts have been made to understand the level of underlying paracrine activities influenced by stem cell secreted trophic factors, as little is known about these interactions. Recent findings, however, elucidate this role by reporting the effects of stem cell derived extracellular vesicles (EVs) that mimic the phenotypes of the cells from which they originate. Exchange of genetic information utilizing persistent bidirectional communication mediated by stem cell-EVs could regulate stemness, self-renewal, and differentiation in stem cells and their subpopulations. This review therefore discusses stem cell-EVs as evolving communication factors in stem cell biology, focusing on how they regulate cell fates by inducing persistent and prolonged genetic reprogramming of resident cells in a paracrine fashion. In addition, we address the role of stem cell-secreted vesicles in shaping the tumor microenvironment and immunomodulation and in their ability to stimulate endogenous repair processes during tissue damage. Collectively, these functions ensure an enormous potential for future therapies.

Leukemic CD34+CD38- Cells Display Conserved Differential Expression of Many ATP Binding-Cassette Transporter Genes.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1380-1380
Author(s):  
Marc H.G.P. Raaijmakers ◽  
Elke P.L.M. de Grouw ◽  
Louis T.F. van de Locht ◽  
Bert A. van der Reijden ◽  
Theo J.M. de Witte ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Stem Cell ◽  
Abc Transporters ◽  
Cell Biology ◽  
Cell Fraction ◽  
Atp Binding ◽  
Stem Cell Biology ◽  
Hematopoietic Stem ◽  
Atp Binding Cassette

Abstract In most cases of acute myeloid leukemia (AML) CD34+CD38− cells are considered to be stem cells, responsible for the maintenance and relapse of AML. ATP binding cassette transporters function in the extrusion of xenobiotics and chemotherapeutical compounds, and may be involved in therapy resistance. Elucidation of mechanisms conferring drug resistance to CD34+CD38− cells is essential to provide novel targets for stem cell eradication in AML. We studied gene expression of all 45 transmembrane ABC transporters (the complete ABCA, B, C, D and G family) in human hematopoietic CD34+CD38− cells and more committed CD34+CD38+ progenitor cells, from healthy donors and patients with non-hematological diseases (N=11) and AML patients (N=11). Gene expression was assessed using a novel real-time RT-PCR approach with micro fluidic cards. In normal CD34+CD38− cells 36 ABC transporters were expressed, 22 of these displayed significant higher expression in the CD34+CD38− cell fraction compared to the CD34+CD38+ cell fraction. In addition to the known stem cell transporters (ABCB1, ABCC1 and ABCG2) these differential expressed genes included many members not previously associated with stem cell biology. In AML the ABC transporter expression profile was largely conserved, including expression of all 13 known drug transporters. These data suggest an important role for many ABC transporters in hematopoietic stem cell biology. In addition, the preferential expression of a high number of drug transport related transporters predicts that broad spectrum inhibition of ABC transporters is likely to be required for CD34+38− stem cell eradication in AML. This approach will, apart from affecting the leukemic stem cells, equally affect the normal stem cells.

The Role of Nucleophosmin In Hematopoietic Stem Cells and the Pathogenesis of Myelodysplastic Syndrome

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 95-95 ◽  
Author(s):  
Keisuke Ito ◽  
Paolo Sportoletti ◽  
John G Clohessy ◽  
Grisendi Silvia ◽  
Pier Paolo Pandolfi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Myelodysplastic Syndrome ◽  
Cell Biology ◽  
De Novo ◽  
Stem Cell Biology ◽  
Hematopoietic Stem

Abstract Abstract 95 Myelodysplastic syndrome (MDS) is an incurable stem cell disorder characterized by ineffective hematopoiesis and an increased risk of leukemia transformation. Nucleophosmin (NPM) is directly implicated in primitive hematopoiesis, the pathogenesis of hematopoietic malignancies and more recently of MDS. However, little is known regarding the molecular role and function of NPM in MDS pathogenesis and in stem cell biology. Here we present data demonstrating that NPM plays a critical role in the maintenance of hematopoietic stem cells (HSCs) and the transformation of MDS into leukemia. NPM is located on chromosome 5q and is frequently lost in therapy-related and de novo MDS. We have previously shown that Npm1 acts as a haploinsufficient tumor suppressor in the hematopoietic compartment and Npm1+/− mice develop a hematologic syndrome with features of human MDS, including increased susceptibility to leukemogenesis. As HSCs have been demonstrated to be the target of the primary neoplastic event in MDS, a functional analysis of the HSC compartment is essential to understand the molecular mechanisms in MDS pathogenesis. However, the role of NPM in adult hematopoiesis remains largely unknown as Npm1-deficiency leads to embryonic lethality. To investigate NPM function in adult hematopoiesis, we have generated conditional knockout mice of Npm1, using the Cre-loxP system. Analysis of Npm1 conditional mutants crossed with Mx1-Cre transgenic mice reveals that Npm1 plays a crucial role in adult hematopoiesis and ablation of Npm1 in adult HSCs leads to aberrant cycling and followed by apoptosis. Analysis of cell cycle status revealed that HSCs are impaired in their ability to maintain quiescence after Npm1-deletion and are rapidly depleted in vivo as well as in vitro. Competitive reconstitution assay revealed that Npm1 acts cell-autonomously to maintain HSCs. Conditional inactivation of Npm1 leads to an MDS phenotype including a profoundly impaired ability to differentiate into cells of the erythroid lineage, megakaryocyte dyspoiesis and centrosome amplification. Furthermore, Npm1 loss evokes a p53-dependent response and Npm1-deleted HSCs undergo apoptosis in vivo and in vitro. Strikingly, transfer of the Npm1 mutation into a p53-null background rescued the apoptosis of Npm1-ablated HSCs and resulted in accelerated transformation to an aggressive and lethal form of acute myeloid leukemia. Our findings highlight the crucial role of NPM in stem cell biology and identify a new mechanism by which MDS can progress to leukemia. This has important therapeutic implications for de novo MDS as well as therapy-related MDS, which is known to rapidly evolve to leukemia with frequent loss or mutation of TRP53. Disclosures: No relevant conflicts of interest to declare.

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