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At least 595 records · Page 33Linked to original sources
PubMed1996

Lineage commitment of CD34+ human hematopoietic progenitor cells.

Hematopoietic cells occur in a continuum of many different stages of functional differentiation, from totipotential stem cells to terminally differentiated lineage-specific cells. At some point during differentiation, progenitor cells become committed to a particular lineage. Little is known about the surface molecules that distinguish lineage-committed progenitor cells from multipotential progenitor cells; this study was undertaken to address this issue. Exploiting a thymic stromal cell co-culture system, we show that CD34+ bone marrow cells expressing the T lymphocyte-associated CD2 and CD7 molecules, the B lymphocyte-associated CD10 and CD19, or the myeloid-associated CD33, contain progenitor cells that can generate T lymphocytes, granulocytes, and monocytes, indicating that the expression of any of these molecules on progenitor cells does not imply lineage commitment. CD34+CD13bright, CD34+CD14+, and CD34+CD15+ cells generated myeloid progeny, and CD34+CD20+ cells failed to differentiate along the T lymphoid and myeloid lineages. Thus expression of CD13, which precedes that of CD14 and CD15 during early hematopoiesis, appears to coincide with commitment to myeloid development. Our findings also indicate that expression of CD20 is restricted to progenitor cells committed to B lymphocyte development.

Adult↗
PubMed1996

Smooth Muscle Lineage Diversity in the Chick Embryo

Lineage analysis studies in the avian embryo have identified two types of smooth muscle cells (SMCs) in the tunica media of large elastic arteries; one that originates within the cardiac neural crest and is ectoderm in origin (Ect) and another that arises from local mesenchyme of mesodermal origin (Mes). To determine if differences in primary embryonic lineage can give rise to SMCs with stable differences in growth and differentiation properties, we isolated Ect and Mes SMCs from the Day 14 chick embryo aorta. We report that despite different primary embryonic origins, Ect and Mes SMCs express nearly identical levels of seven SMC differentiation markers in vitro, consistent with their common smooth muscle developmental fates in vivo. By contrast, Ect SMCs displayed a greater capacity for growth in serum-free medium than Mes SMCs, but only under conditions permitting short-range cell-cell interactions. Most of the peptide growth factors tested that might account for serum-independent growth (PDGF-AA, PDGF-BB, basic FGF, EGF, or activin) stimulated DNA synthesis to similar extents in Ect and Mes SMCs. However, we found dramatic, lineage-dependent differences in SMC responses to transforming growth factor-beta (TGF-beta). Exposure to TGF-beta1 (0.4 to 400 pmole/liter) consistently increased DNA synthesis in Ect SMCs, whereas in paired cultures of Mes SMCs, TGF-beta1 was growth inhibitory. In SMC cultures transfected with p3TP-lux, a luciferase reporter controlled by the TGF-beta1-response elements of the human PAI-1 promoter, TGF-beta1 (120 pM) produced 12 ± 2-fold increases in luciferase activity in Ect SMCs and only 3 ± 1.5-fold increases in Mes SMCs. Analysis of TGF-beta receptor phenotypes by Northern blot, radioligand binding, and crosslinking assays showed that Ect and Mes SMCs expressed similar levels of types I, II, and III TGF-beta receptors. However, using a polyclonal antibody specific for the chick type II TGF-beta receptor subunit, we demonstrate that Mes SMCs produce a fully glycosylated form of this protein while Ect SMCs elaborate only an unglycosylated type II TGF-beta receptor. These results show that Ect and Mes SMCs exhibit lineage-dependent differences in growth and receptor-mediated transcriptional responses to at least one important class of SMC morphogens and growth modifiers, e.g., the TGF-betas. Our findings suggest that different SMC populations within a common vessel wall may respond in lineage-dependent ways to signals that direct formation of the tunica media in the embryo and to factors involved in the progression of vascular disease later in life.

Journal Article↗
PubMed1996

[Epstein-Barr virus (EBV)-positive NK cell line YT, and ALL/LBL of NK-lineage].

The YT cells, already known as natural killer (NK) line, were tested for Epstein-Barr virus (EBV). The simply maintained YT cells (YT-O) and the two different subclones showed and identical length of junctional DNA of terminal repeats in Southern blot with LMP-1 probe, indicating that the 3 had already been positive for EBV before subcloning. YT-O expressed limited amount of EBNA2 or LMP-1 mRNA, whereas the 2 subclones expressed abundant EBNA2 or LMP-1 mRNA in the Northern blot analysis with EBNA2 or LMP-1 probe. Thus, the ex vivo cells were positive for EBV, since the BL (Burkitt lymphoma) type EBV gene expression in the YT-O does not generally occur in in vitro infection. The remaining clinical record indicated that the lymphoma was extranodal (angiocentric lymphoma), involving mediastinum and liver, but not nodal or lymphoblastic lymphoma (LBL). Acute lymphoblastic lymphoma (ALL)/LBL of the NK-lineage has not been defined, although such neoplasms should exist. Since T- and NK-lineages are so close in immature stages of differentiation that ALL/LBL of NK may have been sorted into T-lineage. The phenotypic records of the T-ALL/LBL in our laboratory indicated that CD7+CD5+CD2- is much higher in incidence than CD7+CD5-CD2+. This may reflect the size difference of physiological populations of T- and NK-lineage cells. Furthermore, the latter is of CD45RO type in contrast to the rest of the early-thymic (pro-thymic) T-ALL/LBL groups of CD45RA type. A CD56+ case of 4 CD7+CD5-CD2+ cases have been published as a case of LBL of NK-lineage. It is necessary to scrutinize CD7+CD5-CD2+ cells in order to clarify the phenotype of neoplastic and physiological NK cells in immature stages.

Adolescent↗
PubMed1998

Presence of progenitors restricted to T, B, or myeloid lineage, but absence of multipotent stem cells, in the murine fetal thymus.

The most immature population of fetal thymus (FT) cells has been shown to generate not only T but also B and myeloid cells. The present study was undertaken to clarify whether such a multipotent activity of the earliest population of FT cells is attributed to multipotent hemopoietic progenitors or to a mixture of lineage-restricted progenitors. Examination of individual FT progenitors by a recently established clonal assay system, which is able to determine the developmental potential of each progenitor toward T, B, and myeloid lineages, elucidated that a large majority of progenitors in FT were restricted to the T cell lineage. Presence of a small number of B or myeloid lineage-restricted progenitors was also disclosed. No multipotent progenitors, however, were detected in FT. These results are consistent with our recent finding that restriction of hemopoietic stem cells to T, B, and myeloid lineages takes place in the fetal liver.

Animals↗
PubMed1998

The immunophenotype of blast transformation of chronic myelogenous leukemia: a high frequency of mixed lineage phenotype in "lymphoid" blasts and A comparison of morphologic, immunophenotypic, and molecular findings.

Immunophenotypic studies have a limited role in the diagnosis of chronic myelogenous leukemia (CML) but are increasingly being used in CML blast transformation (BT). Determination of the cell lineage of CML blasts is clinically important because patients with lymphoid blast transformation have a better response to chemotherapy and longer survival than those with other lineages. We studied the morphologic, cytochemical, immunophenotypic, cytogenetic, and molecular features of 20 patients with Philadelphia chromosome-positive CML and more than 10% blast cells in peripheral blood or bone marrow. The blasts were morphologically heterogeneous. CD33 was expressed in 19 cases (95%), followed by CD13 (85%), CD11c (80%), CD36 (60%), CD117 (40%), and CD15 (30%). Seven cases (35%) had a precursor-B lymphoid immunophenotype, and 13 (65%) had a predominantly myeloid immunophenotype. Of the former group, of which only one had a pure lymphoid phenotype, terminal deoxynucleotidyl transferase (TdT) and CD19 were expressed in 100%, CD10 in 85.7%, and CD20 in 14.3%. Of the latter group, all 13 expressed from 3 to 6 myeloid antigens, with 46.2% myeloperoxidase positive and 69.2% CD61 positive. No cases were interpreted as T lineage, but the T-cell antigens CD3, CD4, CD5, and CD7 were expressed in 5.0, 40.0, 5.3. and 30.0% of all cases, respectively. In most cases, the immunophenotype of the CML blasts could not be predicted from their morphologic features. Polymerase chain reaction showed that 80.0% of the lymphoid group and 37.5% of the myeloid group had immunoglobulin heavy-chain gene rearrangements. The frequent lineage infidelity of the blast cells in CML BT seems to be related to the stem cell origin of this disorder. Such lineage infidelity, however, makes classification of many cases difficult and the significance of and criteria for biphenotypic blast crisis of CML is yet to be determined.

Adult↗
PubMed2026

Case Report: Immune-driven clonal selection underlying lineage switch from B-Precursor acute lymphoblastic leukemia to acute myeloid leukemia following inotuzumab ozogamicin.

Lineage switch (LS), defined as a change in leukemic lineage during the disease course, is a rare but clinically significant event in acute leukemia and is typically associated with poor prognosis. Although LS has been increasingly reported following targeted immunotherapies, the clonal mechanisms underlying this phenomenon remain incompletely understood, particularly in cases without KMT2A rearrangement. We report a case of LS from B-precursor acute lymphoblastic leukemia (BCP-ALL) to acute myeloid leukemia (AML) following treatment with the CD22-targeted antibody-drug conjugate inotuzumab ozogamicin. To elucidate the clonal architecture underlying LS, targeted next-generation sequencing was performed on bone marrow samples obtained at multiple time points throughout the disease course. Genomic analysis demonstrated that the lymphoid and myeloid disease phases shared ancestral genetic alterations but displayed distinct mutational profiles. At the time of LS, TP53 and SMC1A mutations newly emerged, whereas only a subset of mutations detected at ALL relapse was retained. These findings suggest that the AML phase most likely resulted from the selective expansion of a genetically distinct subclone derived from a common progenitor, rather than the direct transdifferentiation of the dominant ALL clone, consistent with immunotherapy-driven clonal selection. Longitudinal genomic profiling revealed stepwise clonal evolution during disease progression, supporting a model of immunotherapy-driven clonal selection leading to LS. This case provides molecular evidence suggesting that immune-targeted therapy can promote expansion of minor pre-existing subclones with alternative lineage potential within a common progenitor even in non-KMT2A-rearranged leukemia. Our findings highlight the importance of comprehensive genomic monitoring during immunotherapy to identify therapy-resistant subclones and better understand mechanisms of lineage plasticity in acute leukemia.

Humans↗
PubMed1996

Disruption of mesectodermal lineages by temporal misexpression of the Drosophila POU-domain transcription factor, drifter.

Among the first cells to differentiate in the Drosophila ventral nerve cord, the mesectodermal (midline) lineage gives rise to a discrete set of neurons and glia previously demonstrated to play an important role in the organization of the developing nervous system. The relative simplicity of the midline has allowed the elucidation of many aspects of initial lineage commitment and subsequent differentiation. Based upon its mesectodermal expression pattern and loss-of-function phenotype, we have proposed a key role for the Drosophila POU-domain transcription factor, drifter (dfr), in mesectodermal lineage development. In this study, we have examined the developmental consequences of dfr misexpression using transgenic lines expressing wild-type Drifter protein under control of the heat-inducible hsp70 promoter. Induction of ubiquitous DFR protein during a restricted period of embryogenesis causes a defective axonal phenotype characterized by failure of commissure formation. Based on examination of cell-specific markers for mesectodermal cells, these defects appear to be the result of a suppression of single-minded expression resulting in the disruption of mesectodermal lineage designation and differentiation. The observed temporally restricted sensitivity to DFR expression suggests possible interactions between DFR protein and other stage-specific mesectodermal regulatory factors present before or after a defined mesectodermal developmental event.

Animals↗
PubMed1999

An influence of CD5 on the selection of CD4-lineage T cells.

Combining CD5-null, MHC-deficient and lineage-specific reporter animals, we have investigated the influence of CD5 on positive selection and the choice of CD4- versus CD8-lineage commitment on broad populations of thymocytes. CD5 has no obvious quantitative effect in wild-type mice. In mice lacking MHC class II molecules, however, increased numbers of transitional, class I-selected CD4+ CD8(int) CD3(hi) cells were positively selected in the absence of CD5. Importantly, they were committed to the CD4 lineage. Our results indicate that CD5 negatively regulates the differentiation of CD4-committed cells in suboptimal conditions, thus perhaps serving to tighten the correlation between restriction of the TCR and lineage choice.

Animals↗
PubMed1995

The cell lineage of neuronal subtypes in the mammalian cerebral cortex.

We have studied the lineage relationships of pyramidal and nonpyramidal neurons, the principal neuronal types in the cerebral cortex, using a recombinant retrovirus that carries the gene encoding Escherichia coli beta-galactosidase as a lineage marker. The phenotype of every cell of clones of beta-galactosidase-labelled neurons generated by intraventricular injection of recombinant retrovirus in rat embryos at different stages of cortical neurogenesis was identified using light and electron microscopy as well as immunohistochemistry for known markers of neuronal subtypes. We found that clonally related neurons in adult rats showed the same morphological and neurotransmitter phenotypes, suggesting that lineages of pyramidal and nonpyramidal neurons are specified as early as E14, the time of onset of neurogenesis. However, when we followed the development of cortical cell lineages, we noted that a significant number of neuronal clones showed a mixed pyramidal/nonpyramidal cell composition during the first three weeks of life. We suggest that the change in the composition of neuronal clones between the third week of postnatal life and adulthood may either be due to changes in the phenotype of some developing neurons or, more likely, to selective cell death.

Animals↗
PubMed2003

Recruitment of intra- and extracardiac cells into the myocardial lineage during mouse development.

The tubular heart differentiates from the bilateral cardiac fields in the splanchnic mesoderm. The expression of smooth muscle proteins has been shown to accompany the early phases of cardiac muscle formation. In this study we show that during elongation of the arterial pole of the mouse linear heart tube, alpha-smooth muscle actin (alpha-Sma) expression extends in the area that has been shown to become recruited into the myocardial lineage, but does not yet express myocardial markers. These data suggest that alpha-Sma identifies mesodermal cells that during subsequent development will be recruited into the myocardial lineage. Myocardium formation is not only observed at the arterial pole, but also at the venous pole and in the intracardiac mesenchyme. This results in the formation of the caval and pulmonary myocardium, the smooth-walled atrial myocardium, the myocardial atrioventricular septum, and the myocardial outlet septum. To determine whether recruitment into the myocardial lineage also takes place in these regions, the spatiotemporal pattern of expression of alpha-Sma and of the myocardial markers sarcoplasmatic reticulum calcium ATPase (Serca2a), alpha-myosin heavy chain (Mhc), and beta-Mhc were examined. We show that prior to the expression of myocardial markers, alpha-Sma is expressed in these regions, which suggests that these mesodermal cells become recruited into the cardiac lineage after formation of the linear heart tube.

Actins↗
PubMed2005

Left-right lineage analysis of AV cushion tissue in normal and laterality defective Xenopus hearts.

The majority of complex congenital heart defects occur in individuals who are afflicted by laterality disease. We hypothesize that the prevalence of valvuloseptal defects in this population is due to defective left-right patterning of the embryonic atrioventricular (AV) canal cushions, which are the progenitor tissue for valve and septal structures in the mature heart. Using embryos of the frog Xenopus laevis, this hypothesis was tested by performing left-right lineage analysis of myocytes and cushion mesenchyme cells of the superior and inferior cushion regions of the AV canal. Lineage analyses were conducted in both wild-type and laterality mutant embryos experimentally induced by misexpression of ALK4, a type I TGF-beta receptor previously shown to modulate left-right axis determination in Xenopus. We find that abnormalities in overall amount and left-right cell lineage composition are present in a majority of ALK4-induced laterality mutant embryos and that much variation in the nature of these abnormalities exists in embryos that exhibit the same overall body situs. We propose that these two parameters of cushion tissue formation-amount and left-right lineage origin-are important for normal processes of valvuloseptal morphogenesis and that defective allocation of cells in the AV canal might be causatively linked to the high incidence of valvuloseptal defects associated with laterality disease.

Activin Receptors↗
PubMed2006

The role of early lineage in GABAergic and glutamatergic cell fate determination in Xenopus laevis.

Proper functioning of the adult nervous system is critically dependent on neurons adopting the correct neurotransmitter phenotype during early development. Whereas the importance of cell-cell communication in fate determination is well documented for a number of neurotransmitter phenotypes, the contributions made by early lineage to this process remain less clear. This is particularly true for gamma-aminobutyric acid (GABA)ergic and glutamatergic neurons, which are present as the most abundant inhibitory and excitatory neurons, respectively, in the central nervous system of all vertebrates. In the present study, we have investigated the role of early lineage in the determination of these two neurotransmitter phenotypes by constructing a fate map of GABAergic and glutamatergic neurons for the 32-cell stage Xenopus embryo with the goal of determining whether early lineage influences the acquisition of these two neurotransmitter phenotypes. To examine these phenotypes, we have cloned xGAT-1, a molecular marker for the GABAergic phenotype in Xenopus, and described its expression pattern over the course of development. Although we have identified isolated examples of a blastomere imparting a statistically significant bias, when taken together, our results suggest that blastomere lineage does not impart a widespread bias for subsequent GABAergic or glutamatergic fate determination. In addition, the fate map presented here suggests a general dorsal-anterior to ventral-posterior patterning progression of the nervous system for the 32-cell stage Xenopus embryo.

Animals↗
PubMed1999

Maturation decreases responsiveness of human bone marrow B lineage cells to stromal-derived factor 1 (SDF-1).

We compared the chemotactic responsiveness of different subsets of human B lineage cells to stromal derived factor-1 (SDF-1). High percentages (30-40% of input) of purified bone marrow progenitors including non-B lineage progenitors, pro-B cells, and pre-B cells migrated to SDF-1alpha, demonstrating that SDF-1 is an efficacious chemoattractant of these cells. Pro-B cells responded optimally to a lower concentration of SDF-1 than other subsets, demonstrating that SDF-1 is a more potent chemoattractant of this subset. A lower percentage (10-15% of input) of mature B lymphocytes migrated to SDF-1alpha than pro-B cells, demonstrating that responsiveness of B lineage cells to SDF-1 decreases during differentiation. Inhibition by anti-CXCR4 mAb demonstrated that migration of B lineage cells to SDF-1 was completely dependent on CXC chemokine receptor-4 (CXCR4). Mature B cells expressed higher levels of CXCR4 receptors than uncommitted progenitors and pro-B cells, despite differences in responsiveness to SDF-1. CXCR4 receptors expressed by unresponsive and SDF-1-responsive B cells bound SDF-1alpha with similar affinities (K(D) = 1.7-3.3 x 10(-9) M). Therefore, elements downstream from CXCR4 appear to regulate responsiveness of B cells to SDF-1. We speculate that SDF-1 and CXCR4 direct migration of progenitor cells in microenvironments that promote B lymphopoiesis.

B-Lymphocytes↗
PubMed1996

In vitro differentiation of murine Sca-1+Lin- cells into myeloid, B cell and T cell lineages.

Hematopoietic progenitor cells were shown to be capable of differentiating into myeloid, B cell and T cell lineages. We used a two-step culture system in which enriched murine hematopoietic progenitors in bone marrow were first plated in viscid culture medium containing methylcellulose, erythropoietin (EPO), stem cell factor (SCF) and interleukin (IL)-7. One thousand enriched murine marrow cells formed 53.5 +/- 12.1 (mean +/- SD) primary colonies. Cells from a single blast colony were separated into two aliquots and replated in secondary methylcellulose cultures containing SCF and IL-7 for B cell lineage and SCF, IL-3, G-CSF, GM-CSF and EPO for myeloid lineage. Next, cells from five to ten primary blast colonies were cultured again in embryonal thymus (25 Gy irradiated). One aliquot of blast colonies in a primary culture contained four colony forming units (CFU) of granulocytes, erythroblasts, macrophages and megakaryocytes, eight CFU-granulocytes and macrophages, and 28 BFU-E in a representative secondary myeloid culture. Another aliquot formed a few B cell colonies (2-10) in a secondary B cell culture. B lymphoid colonies were composed of blast-like cells with B-220 antigen. T cells in a secondary T cell culture consisted of 16% L3T4+, 16% CD8+ and 11% CD3+ of bone marrow origin in the thymus. From these results, we concluded that cells in the primary colonies from Sca-1+Lin- hematopoietic stem cells could differentiate into B cell, T cell and myeloid lineages.

Animals↗
PubMed1999

Signals involved in gamma/delta T cell versus alpha/beta T cell lineage commitment.

In seeking an explanation for the complexity of tissue development, biologists are obliged to explain lineage commitment, the events that dictate whether or not a progenitor cell will differentiate into one cell type or another. Such explanations have been sought across a broad spectrum of biological systems, although in no case has a full under- standing been developed. For immunologists, attention has been focused on the lineage commitment of a T cell progenitor to becoming either a gammadelta T cell or an alphabeta T cell. In this review, we compare the signals that thymocytes may receive from the pre T cell receptor (preTCR) with signalling from TCRgammadelta. These signals may determine, co-determine, facilitate, or cement the alphabeta/gammadelta lineage decision, in concert with signals from additional molecules, such as Notch and cytokine receptors. Elucidating the pleiotropic signalling events, particularly those elicited by the preTCR, may in the near future contribute to a molecular definition of lineage commitment.

Animals↗
PubMed1999

Hypothesis: genes which function in a stochastic lineage commitment process are subject to monoallelic expression.

The collection of genes which are now known to be monoallelically expressed in mammals is a diverse set. In the case of the genes which encode transducing receptors, such as immunoglobulins or odoront receptors, monoallelic expression ensures that cell activity is related to encountering a unique ligand. However, some monoallelically expressed genes do not encode receptors, and in these cases the physiological purpose of monoallelic expression is uncertain. Even more puzzling are the cases of imprinted genes, where only the maternal or only the paternal allele is expressed. In this article we consider the hypothesis that some of these cases of monoallelic expression reflect the unusual instances in development in which lineage commitment results from a selective rather than an instructive mechanism. These mechanisms are distinguished by their reliance on either external signals (instructive) or internal, cell autonomous events (selective) to cause the changes in gene expression which correspond to lineage commitment. While the instructive mechanism predicts that lineage commitment genes will be expressed or silenced biallelically, the selective mechanism predicts that commitment genes will be subject to monoallelic expression. Specifically, for the cases in which lineage commitment results from activating gene expression, the selective mechanism predicts that commitment genes will be monoallelically expressed following commitment, such as observed recently for some cytokine and transcription factor genes. For the cases in which extinction of gene expression causes commitment, the selective mechanism predicts that the commitment genes will be monoallelically expressed prior to commitment, as for X-linked and imprinted genes.

Alleles↗
PubMed2005

Helix-loop-helix proteins in lymphocyte lineage determination.

The cells of the lymphoid system develop from multipotent hematopoietic stem cells through a series of intermediate progenitors with progressively restricted developmental options. Commitment to a given lymphoid lineage appears to be controlled by numerous transcriptional regulatory proteins that activate lineage-specific gene expression programs and extinguish expression of lineage-inappropriate genes. In this review I discuss the function of transcription factors belonging to the helix-loop-helix protein family in the control of lymphoid cell fate decisions. A model of lymphocyte lineage determination based on the antagonistic activity of transcriptional activating and repressing helix-loop-helix proteins is presented.

Animals↗
PubMedDate not supplied

Cytokines regulate the cellular phenotype of developing neural lineage species.

The patterns and mechanisms of action of inductive signals that orchestrate neural lineage commitment and differentiation in the mammalian brain are incompletely understood. To examine these developmental issues, we have utilized several culture systems including conditionally immortalized cell lines, subventricular zone progenitor cells and primary neuronal cultures. A neural stem and progenitor cell line (MK31) was established from murine embryonic hippocampus by retroviral transduction of temperature-sensitive alleles of the simian virus 40 large tumor antigen. At the non-permissive temperature for antigen expression (39 degrees C) in serum-free media, the neural stem cells give rise to a series of increasingly mature neuronal progenitor and differentiated cellular forms under the influence of a subset of hematolymphopoietic cytokines (interleukins 5, 7, 9 and 11), when individually co-applied with transforming growth factor alpha, after pretreatment with basic fibroblast growth factor. These cellular forms elaborated a series of progressively more mature neurofilament proteins, a sequential pattern of ligand-gated channels, and inward currents and generation of action potentials with mature physiological properties. Because the factors regulating the development of central nervous system astrocytes have been so difficult to define, we have chosen to focus, in this manuscript, on the elaboration of this cell type. At 39 degrees C, application of a subfamily of bone morphogenetic proteins of the transforming growth factor beta superfamily of growth factors sanctioned the selective expression of astrocytic progenitor cells and mature astrocytes, as defined by sequential elaboration of the Yb subunit of glutathione-S-transferase and glial fibrillary acidic protein. These lineage-specific cytokine inductive relationships were verified using subventricular zone neural progenitor cells generated by the application of epidermal growth factor, alone or in combination with basic fibroblast growth factor, to dissociated cellular cultures derived from early embryonic murine brain, a normal non-transformed developmental population. Finally, application of a different series of cytokines from five distinct factor classes (basic fibroblast growth factor, platelet-derived growth factor-AA, insulin-like growth factor 1, neurotrophin 3 and representative gp130 receptor subunit-related ligands) caused the elaboration of oligodendroglial progenitor species and post-mitotic oligodendrocytes, defined by progressive morphological maturation and the expression of increasingly advanced oligodendroglial and oligodendrocyte lineage markers. In addition, seven different gp130-associated neuropoietic (ciliary neurotrophic factor, leukemia inhibitory factor, oncostatin-M) and hematopoietic (interleukins 6, 11, 12, granulocyte-colony stimulating factor) cytokines exhibited differential trophic effects on oligodendroglial lineage maturation and factor class interactions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗