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PubMed1998

Long-term contribution to the myeloid compartment by lineage-committed stem cells.

The current paradigm concerning the kinetics of hematopoiesis is that only the most primitive pluripotential bone marrow stem cells can support prolonged hematopoiesis whereas more differentiated, lineage-committed stem cells can only contribute to a particular lineage for a limited period of time. In this study, we present evidence that in mice, the spleen contains a long-lived myeloid-committed stem cell population(s) that continuously replenishes the mature myeloid lineage for at least 9 months. After myeloid-specific retroviral-mediated gene transfer, the exogenous gene could be detected in thioglycollate-induced macrophages and granulocytes by Southern blot analysis and by in situ polymerase chain reaction on an individual cell basis. The targeted stem cell population does not repopulate the bone marrow in secondary recipients and did not give rise to cells other than cells of the myeloid lineage. It therefore represents the first nonpluripotential stem cell population capable of replenishing a hemopoietic lineage for a long period of time. The ability to target a myeloid-specific stem cell could facilitate gene therapy of congenital disorders of the myeloid system such as lysosomal storage diseases. It also offers a unique opportunity to assess the immunologic consequences of expressing an exogenous gene of choice exclusively in the myeloid lineage.

Animals↗

PubMed1999

Single adult human CD34(+)/Lin-/CD38(-) progenitors give rise to natural killer cells, B-lineage cells, dendritic cells, and myeloid cells.

Marrow stromal cultures support adult CD34(+)/Lin-/HLA-DR- or CD34(+)/Lin-/CD38(-) cell differentiation into natural killer (NK) or myeloid cells, but unlike committed lymphoid progenitors (CD34(+)/Lin-/CD45RA+/CD10(+)), no B cells are generated. We tested whether different microenvironments could establish a developmental link between the NK and B-cell lineages. Progenitors were cultured in limiting dilutions with interleukin-7 (IL-7), flt3 ligand (FL), c-kit ligand (KL), IL-3, IL-2, and AFT024, a murine fetal liver line, which supports culture of transplantable murine stem cells. NK cells, CD10(+)/CD19(+) B-lineage cells and dendritic cells (DC) developed from the same starting population and IL-7, FL, and KL were required in this process. Single cell deposition of 3,872 CD34(+)/Lin-/CD38(-) cells onto AFT024 with IL-7, FL, KL, IL-2, and IL-3 showed that a one time addition of IL-3 at culture initiation was essential for multilineage differentiation from single cells. Single and double lineage progeny were frequently detected, but more importantly, 2% of single cells could give rise to at least three lineages (NK cells, B-lineage cells, and DC or myeloid cells) providing direct evidence that NK and B-lineage differentiation derive from a common lymphomyeloid hematopoietic progenitor under the same conditions. This study provides new insights into the role of the microenvironment niche, which governs the earliest events in lymphoid development.

ADP-ribosyl Cyclase↗

PubMed1995

Evolution of cell lineage and pattern formation in the vulval equivalence group of rhabditid nematodes.

During the formation of the vulva in many nematode hermaphrodites or females, pattern formation, induction, and cell specification can readily be studied at a single-cell level. Nematodes thus allow an evolutionary analysis of developmental processes. We have analyzed cell lineages and pattern formation in the vulva equivalence group of six rhabditid nematodes of the genera Oscheius, Rhabditella, Rhabditoides, Pelodera, and Protorhabditis. The comparison of these species with four previously analyzed species of this family reveals evolutionary modification at several levels. The number of vulva precursor cells (VPCs) differ among species. Of the three particular cell lineages (1 degree, 2 degrees, and 3 degrees) generated by the vulva precursor cells in Caenorhabditis, two (2 degrees and 3 degrees) are altered, whereas the third lineage (1 degree) is conserved among the analyzed species. While most vulval lineages are invariant, we observe variability of the 3 degrees lineage in Pelodera with respect to the number of precursor cells adopting this fate and the number of progeny formed. In two species, the 3 degrees lineage generates an asymmetrical set of cells, oriented by the gonad. In Protorhabditis we frequently find animals with an additional or altered set of VPCs forming vulval tissue.

Animals↗

PubMed1995

Expression of the Drosophila gooseberry locus defines a subset of neuroblast lineages in the central nervous system.

The development of the central nervous system is known to require lineage-specific factors that are expressed in neuroblasts and their descendants, as well as molecules involved in cell-cell signaling mechanisms. The transcription factors encoded by the gooseberry locus appear to be required for the proper specification of neuroblasts and their lineages. To examine whether gooseberry expression is lineage-specific, we have utilized the FLP recombinase of yeast to positively mark cell lineages throughout Drosophila development. In this system, the actin5C promoter and the lacZ gene are separated by a polyadenylation signal flanked by two direct repeat FRTs. A heat shock is used to induce a pulse of FLP recombinase which catalyzes a site-specific recombination event between the FRT sites. The resulting excision of the polyadenylation site allows expression of lacZ from the actin5C promoter. The descendants of a cell which has undergone a recombination event are now positively marked, enabling us to compare cell lineages with the pattern of gooseberry gene expression. We find that the expression of the gooseberry locus is lineage-specific, suggesting that gooseberry may function as a selector gene in the patterning of the Drosophila central nervous system.

Actins↗

PubMed1995

Tenascin-C induction in Whitlock-Witte culture: a relevant role of the thiol moiety in lymphoid-lineage differentiation.

The extracellular matrix (ECM) glycoprotein tenascin-C is expressed in a temporally and spatially restricted pattern during embryogenesis and carcinogenesis in association with stromal-epithelial interactions. First, we investigated the production of tenascin-C and other ECM glycoproteins in the established in vitro model system specific for the lymphoid-lineage hemopoiesis, i.e., the Whitlock-Witte (W-W) culture system. In murine primary long-term bone marrow cultures, tenascin-C was produced constitutively and was expressed significantly in higher amounts in this system than in the other established in vitro model system specific for the myeloid-lineage hemopoiesis, i.e., the Dexter culture system. 2-Mercaptoethanol (2-ME), a component of the W-W system, induced the secretion of tenascin-C and upregulated the expression of its mRNA. Furthermore, the reduced glutathione, which, like 2-ME, contains a thiol moiety, induced tenascin-C glycoprotein and its mRNA. By contrast, hydrocortisone (HC), a component of the Dexter system, inhibited the secretion of ECM glycoproteins. 2-ME and TGF-beta 1, the latter of which is known as an inducer of ECM glycoproteins, had an additive effect on the induction of tenascin-C when they were simultaneously added to the W-W system. The TGF-beta receptor binding analysis demonstrated that this induction by 2-ME was not mediated by the cell-surface TGF-beta receptors, suggesting that it was regulated independently of TGF-beta 1. Then, the role of thiol compounds in the lymphoid-lineage differentiation was examined. The omission of 2-ME from the W-W system completely eliminated its ability to support the lymphoid-lineage differentiation. Glutathione, which, unlike 2-ME, does not passively permeate through the plasma membrane, did not support the development of a lymphoid lineage. These results indicate that 2-ME, essential for the lymphoid-lineage differentiation in the W-W culture system, is a potent inducer of tenascin-C expression in vitro.

Animals↗

PubMed1998

Isolation and characterization of immature oligodendrocyte lineage cells.

Using in vitro systems, the proliferation, migration, differentiation, and survival of immature oligodendrocyte lineage cells can be examined to elucidate the cellular and molecular interactions that regulate this lineage. The ability to monitor progressive stages of differentiation within the lineage by immunophenotyping and to manipulate the cellular responses with growth factors makes these cultures advantageous as both a method for studying the cell biology of myelination and as a model system for lineage analysis in the mammalian central nervous system. In addition, cultured oligodendrocytes carry out the normal in vivo sequence of expression of a set of cell type-specific genes, some of which are extremely highly expressed, and so provide advantages for analysis of gene regulation. This paper describes commonly used methods for the preparation of mixed glial cell cultures from perinatal rodent brain. Although these cultures are most commonly derived from perinatal rat brain, a protocol for preparation from mouse brain is also provided because of the increasing number of studies that use mice to facilitate molecular biological techniques. Methods to prepare secondary cultures of different stages of oligodendrocyte lineage cells are detailed. As examples of methods to use for the characterization of these cells, immunophenotypes of each stage of the oligodendrocyte lineage are illustrated, incorporation of [3H]thymidine for analysis of cell proliferation is illustrated, and detailed methods are provided for analysis of migration in a microchemotaxis chamber.

Adult↗

PubMed1994

Do the CD4 and CD8 lineages represent parallel pathways?

It is now well established that the progression of T cell development requires interactions between the surfaces of thymocytes and thymic stromal cells. For example, the maturation of CD4+8+ cells into functional CD4+ or CD8+ cells requires TCR/MHC interactions, which, depending on the specificity of the particular TCR, direct the thymocyte to the appropriate lineage. Beyond this, little is known about the molecular mechanism of this lineage choice. Here we describe our recent studies of CD4/CD8 lineage commitment using TCR transgenic mice expressing a well-defined MHC class II specific TCR. While the results of these experiments are inconsistent with a model in which CD4 versus CD8 lineage is determined by an initial TCR/MHC/co-receptor interaction, they also do not support a simple stochastic model of lineage commitment. Instead, we suggest that the CD4 and CD8 lineage may not represent equivalent pathways of T cell maturation. Additionally, we draw several parallels between stochastic models in positive selection and in hematopoiesis.

Animals↗

PubMed2002

Reappearance and global spread of variants of influenza B/Victoria/2/87 lineage viruses in the 2000-2001 and 2001-2002 seasons.

Two antigenically and genetically distinct lineages of influenza B viruses, represented by the reference strains B/Victoria/2/1987 and B/Yamagata/16/1988, have cocirculated in humans since at least 1983. Between 1992 and 2000, Victoria lineage viruses were detected only in eastern Asia. From March to September of 2001 and during the 2001-2002 influenza season, Victoria lineage viruses were detected for the first time in a decade in several countries including Canada, USA, Italy, Netherlands, Norway, Philippines, India, and Oman. Phylogenetic analysis of the hemagglutinin (HA) gene of these viruses revealed that the viruses fell into two distinct clades: one group, represented by the reference strain B/Hong Kong/330/2001, contained viruses sharing three signature amino acids, Arg116, Asn121, and Glu164, while the other group of viruses, represented by B/Oman/16296/2001, shared Thr121 compared to the previous reference strain, B/Shandong/7/97. A number of the viruses in the latter group have been found to be reassortants having a Victoria lineage HA and a Yamagata lineage NA. In the current 2001-2002 season, Victoria-like viruses have now been associated with outbreaks in Asia, Europe, and North America. The reemergence of these Victoria lineage viruses worldwide, the fact that the majority of the B/Victoria-like isolates have poor cross-reactivity to B/Sichuan/379/99-like viruses in current vaccines, and the lack of exposure of young children in many areas of the world to these viruses has resulted in a World Health Organization Northern Hemisphere recommendation for the inclusion of a B/Victoria-like strain in vaccines for the 2002-2003 influenza season.

Animals↗

PubMed2006

Expansion of symmetric exon-bordering domains does not explain evolution of lineage specific genes in mammals.

In order to examine the evolution of lineage specific genes, we analyzed intron phase distributions and exon-bordering domains in primate and rodent specific genes. We found that the expansion of symmetric exon-bordering domains could not explain the evolution of lineage specific genes. Rather internal intron loss of a domain can partially explain the excess of class 1-1 intron phases in the lineage specific genes. We suggest the event that led to excess of symmetric exons in lineage specific genes had little bearing on shaping the phenotypes specific to the individual lineage. Instead, Kruppel-associated box (KRAB) proteins associated with zinc finger C2H2 (zf-C2H2) type are likely to be responsible for the lineage specific function.

Animals↗

PubMed1990

Novel origins of lineage founder cells in the direct-developing sea urchin Heliocidaris erythrogramma.

The lineage and fate of each blastomere in the 32-cell embryo of the direct-developing sea urchin Heliocidaris erythrogramma have been traced by microinjection of tetramethylrhodamine-dextran. The results reveal substantive evolutionary modifications of the ancestral cell lineage pattern of indirect sea urchin development. Significant among these modifications are changes in the time and order of cell lineage segregation: vegetal ectodermal founder cells consistently arise earlier than during indirect development, while internal founder cells generally segregate later and in a different sequence. Modifications have also arisen in proportions of the embryo fated to become various cell types and larval structures. Ectodermal fates, particularly vestibular ectoderm, comprise a greater proportion of the total cellular volume in H. erythrogramma. Among internal cell types, coelom consumes more and endoderm less of the remaining cellular volume than during indirect sea urchin development. Evolutionary modifications are also apparent in the positional origin of larval cell types and structures in H. erythrogramma. These include an apparent tilt in the axis of prospective cell fate relative to the animal-vegetal axis as defined by cleavage planes. Together these evolutionary changes in the cell lineage of H. erythrogramma produce an accelerated loss of dorsoventral symmetry in cell fate relative to indirect development. The extent and diversity of rearrangements in its cell lineage indicate that the non-feeding larva of H. erythrogramma is a highly modified, novel form rather than a degenerate pluteus larva. These same modifications underscore the evolutionarily flexible relationship between cell lineage, gene expression, and larval morphology in sea urchin development.

Animals↗

PubMed1988

Mesodermal cell lineage determination and proto-oncogene expression.

Previously, we have established a rat embryo fibroblastic cell line that is characterized as immortal, nontumorigenic and retains a diploid karyotype. We report here that this cell line will spontaneously differentiate along mesodermal cell lineages to form myotubes and adipocytes. We have isolated and characterized lineage-determined (nondifferentiated) preadipocytes and myoblasts. Using these cell lines we have investigated the expression of proto-oncogenes concomitant with lineage-specific determination. No major changes in proto-oncogene RNA levels were observed that correlated with lineage determination. These results would suggest that none of the 15 proto-oncogenes used in these experiments are involved in mesodermal lineage determination; but this does not rule out the possibility that other proto-oncogenes not tested or currently unknown may be involved. However, these differentiating subclones and nondifferentiating fibroblasts that exhibit a normal karyotype will be an excellent model-system to investigate the molecular basis of cell lineage determination.

Adipose Tissue↗

PubMed1995

Asymmetric signaling requirements for thymocyte commitment to the CD4+ versus CD8+ T cell lineages: a new perspective on thymic commitment and selection.

Differentiation of immature CD4+ CD8+ thymocytes into mature CD4+ CD8- and CD4-CD8+ T cells requires that synthesis of one or the other coreceptor molecule be terminated, a process referred to as lineage commitment. The present study has utilized a novel coreceptor reexpression assay to identify lineage commitment in immature thymocytes and has found that the MHC recognition requirements for CD4 commitment and CD8 commitment fundamentally differ from one another. Remarkably, we found that thymocyte commitment to the CD8+ lineage requires MHC class I-dependent instructional signals, whereas thymocyte commitment to the CD4+ lineage is MHC independent and may occur by default. In addition, an unanticipated relationship between lineage commitment and surface phenotype has been identified. These results are incompatible with current concepts and require a new perspective on lineage commitment and positive selection, which we refer to as asymmetric commitment.

Animals↗

PubMed2025

Invasive Streptococcus dysgalactiae subspecies equisimilis compared with Streptococcus pyogenes in Australia, 2011-23, and the emergence of a multi-continent stG62647 lineage: a retrospective clinical and genomic epidemiology study.

BACKGROUND: Streptococcus dysgalactiae subspecies equisimilis (SDSE) is closely related to Streptococcus pyogenes, with overlapping disease manifestations. We compared the clinical and genomic epidemiology of invasive SDSE with invasive S pyogenes across different settings in Australia and phylogenetically contextualised the SDSE sequences within a global cohort of genomes. METHODS: In this retrospective clinical and genomic epidemiology study, cases of invasive SDSE isolated from normally sterile sites were identified and whole-genome sequenced across five hospital networks in temperate southeast Australia (Melbourne and Sydney) and the tropical Top End of the Northern Territory. SDSE disease incidence, case demographics, clinical outcomes, and longitudinal lineage dynamics were compared between southeast Australia and the Top End and to co-collected invasive S pyogenes cases in each region. SDSE genomes and lineages were also contextualised within 1166 global SDSE sequences. Genomic transmission clusters (not necessarily direct transmission) were inferred between isolates from different individuals by single-linkage clustering at a single nucleotide polymorphism threshold of less than or equal to seven for SDSE and less than or equal to five for S pyogenes based on previous transmission analyses. FINDINGS: Between Jan 1, 2011, and Feb 28, 2023, there were 693 invasive SDSE cases and 995 invasive S pyogenes cases. Invasive SDSE occurred almost exclusively in adults. The overall invasive SDSE incidence in southeast Australia was similar to invasive S pyogenes (incidence rate ratio [IRR] 1·15, 95% CI 0·91-1·46; p=0·26) and increased over the study period (IRR 1·06 per year, 95% CI 1·05-1·08; p<0·0001) from 1·30 cases per 10 000 admissions in 2011 to 3·72 cases per 10 000 admissions in the first 2 months of 2023 (95% CI 2·13-6·07). In southeast Australia, where stringent COVID-19 non-pharmaceutical interventions (NPIs) were implemented between 2020 and 2021, the SDSE incidence plateaued during 2020-21 but did not significantly decline (IRR 1·09 compared with 2017-19, 95% CI 0·88-1·35; p=0·47). By contrast, S pyogenes incidence substantially declined in 2020-21 in southeast Australia (IRR 0·35 compared to 2017-19, 95% CI 0·22-0·52; p=0·017). In the Top End, SDSE incidence was lower than S pyogenes (IRR 0·24, 95% CI 0·19-0·31; p<0·0001). However, crude incidence remained higher than southeast Australia (crude IRR 1·24, 95% CI 1·07-1·42; p=0·0037) and disproportionately affected First Nations Australians in the Top End compared with non-First Nations individuals (IRR 3·36, 95% CI 2·33-4·85; p<0·0001). Comparing 2020-21 with 2017-19, there was no decline in SDSE (IRR 1·27, 95% CI 0·73-2·24; p=0·45) or S pyogenes (IRR 0·97, 95% CI 0·80-1·18; p=0·81) incidence in the Top End, which did not implement prolonged stringent COVID-19 NPIs. Analysing the available genomes of invasive cases and in lineages for which more than or equal to five invasive cases occurred, only 24 (6%) of 384 SDSE cases were assigned to genomic transmission clusters, compared with 271 (52%) of 524 S pyogenes cases. An stG62647 lineage encompassed 113 (26%) of 436 sequenced SDSE genomes. Analysis of available SDSE sequences from Australia, western Europe, and North America inferred concurrent international expansion of the stG62647 lineage in all three regions between 1990 and 2005. INTERPRETATION: We identified a substantial burden of invasive SDSE, dominated by the emergent stG62647 lineage. The contrasting epidemiology between species in the different Australian regions, during COVID-19 NPIs, and genomic infection patterns indicates transmission dynamic, pathogen population, and host-pathogen interaction differences between SDSE and S pyogenes and indicates implications for disease control measures. FUNDING: Australian National Health and Medical Research Council.

Humans↗

PubMed2004

Evidence supporting the inclusion of strains from each of the two co-circulating lineages of H3N8 equine influenza virus in vaccines.

Two lineages of antigenically distinct equine influenza A H3N8 subtype viruses, American and European, co-circulate. Experiments were conducted in ponies to investigate the protection induced by vaccines containing virus from one lineage against challenge infection with homologous or heterologous virus. Regression analysis showed that vaccinated ponies with average pre-challenge single radial haemolysis (SRH) antibody levels (i.e. 45-190mm2) had a higher probability of becoming infected if they were vaccinated with virus heterologous to the challenge strain than if they were vaccinated with homologous virus. Field studies in Thoroughbred racehorses also showed that SRH antibody levels of >/= 150mm2 induced by vaccines containing a European lineage strain are protective against infection with a virus from the same lineage, but that the same or higher antibody levels may not be protective against an American lineage virus. In conclusion, vaccines should contain virus strains representative of both H3N8 subtype lineages to maximise protection against infection.

Animals↗

PubMed2002

Phylogeny of New World arenaviruses based on the complete coding sequences of the small genomic segment identified an evolutionary lineage produced by intrasegmental recombination.

Previous studies suggested that the small genomic segments (S-RNA) of the South American arenaviruses (SA-AVs) represent three phylogenetic lineages (designated A, B, and C) and indicated that the S-RNA of Whitewater Arroyo virus (WWAV) (a North American arenavirus [NA-AV]) is a product of genetic recombination between a lineage A and lineage B virus. The purpose of this study was to extend our knowledge on the phylogenetic relationships between WWAV, the two other NA-AVs (Tamiami and bear canyon), and the 15 SA-AVs. Therefore, we determined the complete sequence of the S-RNA of nine arenaviruses previously uncharacterized or sequenced only partially. Phylogenetic analyses of the two complete coding regions indicated that the S-RNA of the three NA-AVs have descended from a single ancestral virus, which was the product of recombination between a lineage A and lineage B arenavirus. No such evidence for genetic recombination was found in cupixi virus (a novel arenavirus isolated from a wild rodent captured in Northeastern Brazil) or the 14 other SA-AVs. The recombinant nature of the S-RNA of NA-AVs distinguishes them from the SA-AVs, and thus, indicates that the NA-AVs represent a fourth phylogenetic lineage in the Tacaribe serocomplex.

Amino Acid Sequence↗

PubMed2003

Serotype C foot-and-mouth disease virus isolates from India belong to a separate so far not described lineage.

Complete 1D gene sequences of 13 Indian foot-and-mouth disease virus (FMDV) type C field isolates and a vaccine strain (C-Bombay/64) were determined. All the field isolates showed a greater genetic homogeneity (95-100%) among themselves and were 19.7-21.2% divergent from the vaccine strain. In the phylogenetic analysis, the Indian field isolates formed a separate lineage (lineage VII) different from the previously identified six lineages (lineage I-VI) in type C FMDV [J. Virol. 66 (1992) 3557]. The vaccine strain was grouped with European lineage (lineage II). Comparison of the deduced amino acid sequences of antigenic sites A and C of field isolates showed no significant variation from the vaccine strain. One-way serological relationship determined in ELISA showed antigenic closeness of the field isolates with C-Bombay/64.

Amino Acid Sequence↗

PubMed1995

Cell lineage patterns and homeotic gene activity during Antirrhinum flower development.

BACKGROUND: Homeotic genes controlling the identity of flower organs have been characterized in several plant species. To determine whether cells expressing these genes are specified to follow particular developmental fates, we have studied the pattern of cell lineages in developing flowers of Antirrhinum. Each flower has four whorls of organs, and progenitor cells of these can be marked at particular stages of development using a temperature-sensitive transposon. This allows the cell lineages in the flower to be followed, as well as giving information about rates of cell division. RESULTS: We show here that, prior to the emergence of organ primordia, cells in the floral meristem have not been allocated organ identities. After this time, lineage restrictions arise between whorls, correlating with the onset of expression of genes that control organ identity. A further lineage restriction appears slightly later on, between the dorsal and ventral surfaces of the petal. Our results further suggest that the rates of cell division fluctuate during key stages of meristern development, perhaps as a consequence of meristem-identity gene expression. CONCLUSIONS: The patterns of lineage restriction and organ-identity gene expression in early floral meristems are consistent with some cells being allocated specific identities at about this stage of development. Plant cells cannot move relative to each other, so lineage restrictions in plants may reflect particular orientations and/or rates of growth at boundary regions.

Genes, Homeobox↗

PubMed1995

O6-methylguanine-DNA methyltransferase in tumors and cells of the oligodendrocyte lineage.

BACKGROUND: Oligodendrogliomas respond to nitrosourea-based chemotherapy and are induced in rats following transplacental exposure to ethylnitrosourea, observations suggesting that neoplastic and normal cells of the oligodendrocyte lineage are "sensitive" to nitrosoureas. Nitrosoureas alkylate DNA at O6-guanine with repair mediated by O6-methylguanine-DNA methyltransferase (MGMT). The cytotoxic and carcinogenic properties of the nitrosoureas appear related to MGMT activity. METHODS: To explore why oligodendrogliomas respond to chemotherapy, we measured MGMT activity in five chemosensitive human oligodendrogliomas and in rat oligodendrocyte lineage cells. We also measured MGMT activity in rat astrocytes and compared the cytotoxic effects of carmustine (BCNU) on oligodendrocyte lineage cells and astrocytes. RESULTS: Low levels of MGMT activity were found in five of five human oligodendrogliomas. Cultures of neonatal rat glia enriched for oligodendrocyte lineage cells also had low levels of MGMT activity, approximately one-third that found in astrocytes (p < 0.02), and oligodendrocyte lineage cells were more sensitive to BCNU than astrocytes. CONCLUSIONS: Low MGMT activity may contribute to the chemosensitivity of some human oligodendrogliomas and rat oligodendrocyte lineage cells also have low levels. If drug resistance mechanisms in tumors reflect the biochemical properties of their cells of origin, then normal glia may serve as a laboratory substitute for human glioma.

Adult↗