scholarly journals Invertebrate Retinal Progenitors as Regenerative Models in a Microfluidic System

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1301 ◽  
Author(s):  
Pena ◽  
Zhang ◽  
Majeska ◽  
Venkatesh ◽  
Vazquez
Keyword(s):  
Progenitor Cells ◽  
Cluster Size ◽  
Cell Types ◽  
Microfluidic System ◽  
Cell Replacement ◽  
Current Article ◽  
Chemotaxis Models ◽  
Invertebrate Model ◽  
Bio Engineering ◽  
Transplantation Outcomes

Regenerative retinal therapies have introduced progenitor cells to replace dysfunctional or injured neurons and regain visual function. While contemporary cell replacement therapies have delivered retinal progenitor cells (RPCs) within customized biomaterials to promote viability and enable transplantation, outcomes have been severely limited by the misdirected and/or insufficient migration of transplanted cells. RPCs must achieve appropriate spatial and functional positioning in host retina, collectively, to restore vision, whereas movement of clustered cells differs substantially from the single cell migration studied in classical chemotaxis models. Defining how RPCs interact with each other, neighboring cell types and surrounding extracellular matrixes are critical to our understanding of retinogenesis and the development of effective, cell-based approaches to retinal replacement. The current article describes a new bio-engineering approach to investigate the migratory responses of innate collections of RPCs upon extracellular substrates by combining microfluidics with the well-established invertebrate model of Drosophila melanogaster. Experiments utilized microfluidics to investigate how the composition, size, and adhesion of RPC clusters on defined extracellular substrates affected migration to exogenous chemotactic signaling. Results demonstrated that retinal cluster size and composition influenced RPC clustering upon extracellular substrates of concanavalin (Con-A), Laminin (LM), and poly-L-lysine (PLL), and that RPC cluster size greatly altered collective migratory responses to signaling from Fibroblast Growth Factor (FGF), a primary chemotactic agent in Drosophila. These results highlight the significance of examining collective cell-biomaterial interactions on bio-substrates of emerging biomaterials to aid directional migration of transplanted cells. Our approach further introduces the benefits of pairing genetically controlled models with experimentally controlled microenvironments to advance cell replacement therapies.

scholarly journals Human leukemia mutations corrupt but do not abrogate GATA-2 function

2018 ◽  
Vol 115 (43) ◽  
pp. E10109-E10118 ◽  
Author(s):  
Koichi R. Katsumura ◽  
Charu Mehta ◽  
Kyle J. Hewitt ◽  
Alexandra A. Soukup ◽  
Isabela Fraga de Andrade ◽  
...  
Keyword(s):  
Dna Binding ◽  
Progenitor Cells ◽  
Zinc Finger ◽  
Erythroid Differentiation ◽  
Cell Types ◽  
Myeloid Differentiation ◽  
Human Leukemia ◽  
Hematopoietic Stem ◽  
Amino Terminal ◽  
Disease Mutations

By inducing the generation and function of hematopoietic stem and progenitor cells, the master regulator of hematopoiesis GATA-2 controls the production of all blood cell types. Heterozygous GATA2 mutations cause immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. GATA2 disease mutations commonly disrupt amino acid residues that mediate DNA binding or cis-elements within a vital GATA2 intronic enhancer, suggesting a haploinsufficiency mechanism of pathogenesis. Mutations also occur in GATA2 coding regions distinct from the DNA-binding carboxyl-terminal zinc finger (C-finger), including the amino-terminal zinc finger (N-finger), and N-finger function is not established. Whether distinct mutations differentially impact GATA-2 mechanisms is unknown. Here, we demonstrate that N-finger mutations decreased GATA-2 chromatin occupancy and attenuated target gene regulation. We developed a genetic complementation assay to quantify GATA-2 function in myeloid progenitor cells from Gata2 −77 enhancer-mutant mice. GATA-2 complementation increased erythroid and myeloid differentiation. While GATA-2 disease mutants were not competent to induce erythroid differentiation of Lin−Kit+ myeloid progenitors, unexpectedly, they promoted myeloid differentiation and proliferation. As the myelopoiesis-promoting activity of GATA-2 mutants exceeded that of GATA-2, GATA2 disease mutations are not strictly inhibitory. Thus, we propose that the haploinsufficiency paradigm does not fully explain GATA-2–linked pathogenesis, and an amalgamation of qualitative and quantitative defects instigated by GATA2 mutations underlies the complex phenotypes of GATA-2–dependent pathologies.

scholarly journals Neural stemness contributes to cell tumorigenicity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Liyang Xu ◽  
Min Zhang ◽  
Lihua Shi ◽  
Xiaoli Yang ◽  
Lu Chen ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Progenitor Cells ◽  
Neural Development ◽  
Ground State ◽  
Cell Types ◽  
Bioinformatic Analysis ◽  
Neural Cells ◽  
Differentiation Potential ◽  
Neural Genes ◽  
Neural Stem Progenitor Cells

Abstract Background Previous studies demonstrated the dependence of cancer on nerve. Recently, a growing number of studies reveal that cancer cells share the property and regulatory network with neural stem/progenitor cells. However, relationship between the property of neural stemness and cell tumorigenicity is unknown. Results We show that neural stem/progenitor cells, but not non-neural embryonic or somatic stem/progenitor cell types, exhibit tumorigenicity and the potential for differentiation into tissue types of all germ layers when they are placed in non-native environment by transplantation into immunodeficient nude mice. Likewise, cancer cells capable of tumor initiation have the property of neural stemness because of their abilities in neurosphere formation in neural stem cell-specific serum-free medium and in differentiation potential, in addition to their neuronal differentiation potential that was characterized previously. Moreover, loss of a pro-differentiation factor in myoblasts, which have no tumorigenicity, lead to the loss of myoblast identity, and gain of the property of neural stemness, tumorigenicity and potential for re-differentiation. By contrast, loss of neural stemness via differentiation results in the loss of tumorigenicity. These suggest that the property of neural stemness contributes to cell tumorigenicity, and tumor phenotypic heterogeneity might be an effect of differentiation potential of neural stemness. Bioinformatic analysis reveals that neural genes in general are correlated with embryonic development and cancer, in addition to their role in neural development; whereas non-neural genes are not. Most of neural specific genes emerged in typical species representing transition from unicellularity to multicellularity during evolution. Genes in Monosiga brevicollis, a unicellular species that is a closest known relative of metazoans, are biased toward neural cells. Conclusions We suggest that the property of neural stemness is the source of cell tumorigenicity. This is due to that neural biased unicellular state is the ground state for multicellularity and hence cell type diversification or differentiation during evolution, and tumorigenesis is a process of restoration of neural ground state in somatic cells along a default route that is pre-determined by an evolutionary advantage of neural state.

scholarly journals Neural stemness contributes to cell tumorigenicity

2020 ◽  
Author(s):  
Liyang Xu ◽  
Min Zhang ◽  
Lihua Shi ◽  
Xiaoli Yang ◽  
Lu Chen ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Progenitor Cells ◽  
Neural Development ◽  
Ground State ◽  
Cell Types ◽  
Bioinformatic Analysis ◽  
Neural Cells ◽  
Differentiation Potential ◽  
Neural Genes ◽  
Neural Stem Progenitor Cells

Abstract Background: Previous studies demonstrated the dependence of cancer on nerve. Recently, a growing number of studies reveal that cancer cells share the property and regulatory network with neural stem/progenitor cells. However, relationship between the property of neural stemness and cell tumorigenicity is unknown.Results: We show that neural stem/progenitor cells, but not non-neural embryonic or somatic stem/progenitor cell types, exhibit tumorigenicity and the potential for differentiation into tissue types of all germ layers when they are placed in non-native environment by transplantation into immunodeficient nude mice. Likewise, cancer cells capable of tumor initiation have the property of neural stemness because of their abilities in neurosphere formation in neural stem cell-specific serum-free medium and in differentiation potential, in addition to their neuronal differentiation potential that was characterized previously. Moreover, loss of a pro-differentiation factor in myoblasts, which have no tumorigenicity, lead to the loss of myoblast identity, and gain of the property of neural stemness, tumorigenicity and potential for re-differentiation. By contrast, loss of neural stemness via differentiation results in the loss of tumorigenicity. These suggest that the property of neural stemness contributes to cell tumorigenicity, and tumor phenotypic heterogeneity might be an effect of differentiation potential of neural stemness. Bioinformatic analysis reveals that neural genes in general are correlated with embryonic development and cancer, in addition to their role in neural development; whereas non-neural genes are not. Most of neural specific genes emerged in typical species representing transition from unicellularity to multicellularity during evolution. Genes in Monosiga brevicollis, a unicellular species that is a closest known relative of metazoans, are biased toward neural cells.Conclusions: We suggest that the property of neural stemness is the source of cell tumorigenicity. This is due to that neural biased unicellular state is the ground state for multicellularity and hence cell type diversification or differentiation during evolution, and tumorigenesis is a process of restoration of neural ground state in somatic cells along a default route that is pre-determined by an evolutionary advantage of neural state.

scholarly journals Ca(2+) Oscillations and Its Transporters in Mesenchymal Stem Cells

2010 ◽  
pp. 323-329 ◽  
Author(s):  
B Ye
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Replacement Therapy ◽  
Cell Types ◽  
Cell Replacement Therapy ◽  
Cell Replacement ◽  
Cell Functions ◽  
The Past ◽  
Intracellular Ca

Intracellular free Ca(2+) is one of important biological signals regulating a number of cell functions. It has been discussed widely and extensively in several cell types during the past two decades. Attention has been paid to the Ca2+ transportation in mesenchymal stem cells in recent years as mesenchymal stem cells have gained considerable interest due to their potential for cell replacement therapy and tissue engineering. In this paper, roles of intracellular Ca(2+) oscillations and its transporters in mesenchymal stem cells have been reviewed.

Fibroblast progenitor cells of the embryonic chick limb

Development ◽  
1980 ◽  
Vol 56 (1) ◽  
pp. 191-200
Author(s):  
Stuart A. Newman
Keyword(s):  
Progenitor Cells ◽  
Cell Types ◽  
Mesenchymal Cells ◽  
The Other ◽  
Embryonic Chick ◽  
Similar Morphology ◽  
Level Characteristic ◽  
Fibroblast Progenitor Cells ◽  
Wing Tip ◽  
Mesodermal Lineage

A population of mesenchymal cells derived from the stage-25 chick wing tip gives rise to progeny of a similar morphology and to authentic fibroblasts when grown in low densityculture. Mixed clones containing both cell types are often observed. As the more rapidly proliferating fibroblasts begin to predominate in these cultures, collagen biosynthesisrises from the basal mesenchymal level to a level characteristic of mature fibroblasts. Thefibroblast progenitor is discussed relative to the other cell types of the mesodermal lineage of the developing limb.

p57(Kip2) regulates progenitor cell proliferation and amacrine interneuron development in the mouse retina

Development ◽  
2000 ◽  
Vol 127 (16) ◽  
pp. 3593-3605 ◽  
Author(s):  
M.A. Dyer ◽  
C.L. Cepko
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Kinase Inhibitor ◽  
Retinal Development ◽  
Cell Types ◽  
Cell Cycle Exit ◽  
Retinal Progenitor Cells ◽  
Mouse Development ◽  
Retinal Progenitor ◽  
Cyclin Kinase Inhibitor

A precise balance between proliferation and differentiation must be maintained during retinal development to obtain the correct proportion of each of the seven cell types found in the adult tissue. Cyclin kinase inhibitors can regulate cell cycle exit coincident with induction of differentiation programs during development. We have found that the p57(Kip2) cyclin kinase inhibitor is upregulated during G(1)/G(0) in a subset of retinal progenitor cells exiting the cell cycle between embryonic day 14.5 and 16.5 of mouse development. Retroviral mediated overexpression of p57(Kip2) in embryonic retinal progenitor cells led to premature cell cycle exit. Retinae from mice lacking p57(Kip2) exhibited inappropriate S-phase entry and apoptotic nuclei were found in the region where p57(Kip2) is normally expressed. Apoptosis precisely compensated for the inappropriate proliferation in the p57(Kip2)-deficient retinae to preserve the correct proportion of the major retinal cell types. Postnatally, p57(Kip2) was found to be expressed in a novel subpopulation of amacrine interneurons. At this stage, p57(Kip2)did not regulate proliferation. However, perhaps reflecting its role during this late stage of development, animals lacking p57(Kip2) showed an alteration in amacrine subpopulations. p57(Kip2) is the first gene to be implicated as a regulator of amacrine subtype/subpopulation development. Consequently, we propose that p57(Kip2) has two roles during retinal development, acting first as a cyclin kinase inhibitor in mitotic progenitor cells, and then playing a distinct role in neuronal differentiation.

Cell lineage in the rat cerebral cortex: a study using retroviral-mediated gene transfer

Development ◽  
1988 ◽  
Vol 104 (3) ◽  
pp. 473-482 ◽  
Author(s):  
J. Price ◽  
L. Thurlow
Keyword(s):  
Cerebral Cortex ◽  
Progenitor Cells ◽  
Grey Matter ◽  
Cell Lineage ◽  
Cell Types ◽  
Retroviral Vector ◽  
Rat Cerebral Cortex ◽  
Rat Embryos ◽  
Bacterial Enzyme ◽  
Beta Galactosidase

We have used a retroviral vector that codes for the bacterial enzyme beta-galactosidase to study cell lineage in the rat cerebral cortex. This vector has been used to label progenitor cells in the cerebral cortices of rat embryos during the period of neurogenesis. When these embryos are allowed to develop to adulthood, the clones of cells derived from the marked progenitor cells can be identified histochemically. In this way, we can ask what are the lineage relationships between different neural cell types. From these studies, we conclude that there are two distinct types of progenitor cells in the developing cortex. One generates only grey matter astrocytes, whereas the second gives rise to neurones - both pyramidal and nonpyramidal - and to another class of cells that we have tentatively identified as glial cells of the white matter. We have also been able to address the question of how neurones are dispersed in the cortex during histogenesis. It had been previously hypothesized that clonally related neurones migrated radially to form columns in the mature cortex. However, we find that clones of neurones do not form radial columns; rather, they tend to occupy the same or neighbouring cortical laminae and to be spread over several hundreds of micrometers of cortex in the horizontal dimension. This spread occurs in both mediolateral and rostrocaudal directions.

scholarly journals Identification of Split-GAL4 Drivers and Enhancers That Allow Regional Cell Type Manipulations of the Drosophila melanogaster Intestine

Genetics ◽  
2020 ◽  
Vol 216 (4) ◽  
pp. 891-903
Author(s):  
Ishara S. Ariyapala ◽  
Jessica M. Holsopple ◽  
Ellen M. Popodi ◽  
Dalton G. Hartwick ◽  
Lily Kahsai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Expression Patterns ◽  
Cell Types ◽  
Enteroendocrine Cells ◽  
Epithelial Tissue ◽  
Cell Type ◽  
Cell Functions ◽  
Distinct Subset ◽  
Targeted Gene Expression

The Drosophila adult midgut is a model epithelial tissue composed of a few major cell types with distinct regional identities. One of the limitations to its analysis is the lack of tools to manipulate gene expression based on these regional identities. To overcome this obstacle, we applied the intersectional split-GAL4 system to the adult midgut and report 653 driver combinations that label cells by region and cell type. We first identified 424 split-GAL4 drivers with midgut expression from ∼7300 drivers screened, and then evaluated the expression patterns of each of these 424 when paired with three reference drivers that report activity specifically in progenitor cells, enteroendocrine cells, or enterocytes. We also evaluated a subset of the drivers expressed in progenitor cells for expression in enteroblasts using another reference driver. We show that driver combinations can define novel cell populations by identifying a driver that marks a distinct subset of enteroendocrine cells expressing genes usually associated with progenitor cells. The regional cell type patterns associated with the entire set of driver combinations are documented in a freely available website, providing information for the design of thousands of additional driver combinations to experimentally manipulate small subsets of intestinal cells. In addition, we show that intestinal enhancers identified with the split-GAL4 system can confer equivalent expression patterns on other transgenic reporters. Altogether, the resource reported here will enable more precisely targeted gene expression for studying intestinal processes, epithelial cell functions, and diseases affecting self-renewing tissues.

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