B cell development is perturbed in bone marrow from c-<i>fos/v-jun</i> doubly transgenic mice

Fujita, Kenji; Miki, Nobuo; Mojica, Mariluz P.; Takao, Shintaro; Phuchareon, Janyaporn; Nishikawa, Shin‐Ichi; Sudo, Tetsuo; Tokuhisa, Takeshi

doi:10.1093/intimm/5.2.227

Cited by 12 publications

(6 citation statements)

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“…In fact, c-Fos knockout mice showed a marked reduction of B cells in addition to bone formation defects (Wang et al 1992). Overexpression of Fos and Jun in hematopoietic cells also perturbs B-cell development at the pro-B-cell or pre-B-cell stage (Fujita et al 1993). The number of B-cell precursors is increased in Egr1 knockout mice (Gururajan et al 2008), whereas sustained expression of Egr2 in CD2 + lymphocytes causes a severe developmental block in pro-B cells (Li et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells

et al. 2018

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Stem cell fate is orchestrated by core transcription factors (TFs) and epigenetic modifications. Although regulatory genes that control cell type specification are identified, the transcriptional circuit and the cross-talk among regulatory factors during cell fate decisions remain poorly understood. To identify the "time-lapse" TF networks during B-lineage commitment, we used multipotent progenitors harboring a tamoxifen-inducible form of Id3, an in vitro system in which virtually all cells became B cells within 6 d by simply withdrawing 4-hydroxytamoxifen (4-OHT). Transcriptome and epigenome analysis at multiple time points revealed that ∼10%-30% of differentially expressed genes were virtually controlled by the core TFs, including E2A, EBF1, and PAX5. Strikingly, we found unexpected transcriptional priming before the onset of the key TF program. Inhibition of the immediate early genes such as ,, and severely impaired the generation of B cells. Integration of multiple data sets, including transcriptome, protein interactome, and epigenome profiles, identified three representative transcriptional circuits. Single-cell RNA sequencing (RNA-seq) analysis of lymphoid progenitors in bone marrow strongly supported the three-step TF network model during specification of multipotent progenitors toward B-cell lineage in vivo. Thus, our findings will provide a blueprint for studying the normal and neoplastic development of B lymphocytes.

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Section: Discussionmentioning

confidence: 99%

Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells

et al. 2018

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“…Cysteine deficiency of HIV-infected individuals served as a rationale for treatment with N-acetylcysteine (NAC) (Droge et al, 1992). More recently, decreased GSH was correlated with increased levels of oxidized glutathione (GSSG) in HIV-infected CD4 1 T cells, suggesting that a lack of reducing equivalents rather than decreased GSSG synthesis was responsible for GSH deficiency PERL AND BANKI 552 (Buhl et al, 1989;Eck et al, 1989;Jacobson et al, 1990;Droge et al, 1992;Fujita et al, 1993) …”

Section: Evidence For Oxidative Stress Induced By Hivmentioning

confidence: 99%

Genetic and Metabolic Control of the Mitochondrial Transmembrane Potential and Reactive Oxygen Intermediate Production in HIV Disease

Perl

Bánki

2000

Antioxidants & Redox Signaling

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Redox mechanims play important roles in replication of human immunodeficiency virus type 1 (HIV-1) and cellular susceptibility to apoptosis signals. Viral replication and accelerated turnover of CD4+ T cells occur throughout a prolonged asymptomatic phase in patients infected by HIV-1. Disease development is associated with steady loss of CD4+ T cells by apoptosis, increased rate of opportunistic infections and lymphoproliferative diseases, disruption of energy metabolism, and generalized wasting. Such pathological states are preceded by: (i) depletion of intracellular antioxidants, glutathione (GSH) and thioredoxin (TRX), (ii) increased reactive oxygen species (ROS) production, and (iii) changes in mitochondrial transmembrane potential (deltapsi(m)). Disruption of deltapsi(m) appears to be the point of no return in the effector phase of apoptosis. Viral proteins Tat, Nef, Vpr, protease, and gp120, have been implicated in initiation and/or intensification of oxidative stress and disruption of deltapsi(m). Redox-sensitive transcription factors, NF-kappaB, AP-1, and p53, support expression of viral genes and proinflammatory lymphokines. ROS regulate apoptosis signaling through Fas, tumor necrosis factor (TNF), and related cell death receptors, as well as the T-cell receptor. Oxidative stress in HIV-infected donors is accompanied by increased glucose utilization both on the cellular and organismal levels. Generation of GSH and TRX from their corresponding oxidized forms is dependent on NADPH provided through the pentose phosphate pathway of glucose metabolism. This article seeks to delineate the genetic and metabolic bases of HIV-induced oxidative stress. Such understanding should lead to development of effective antioxidant therapies in HIV disease.

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“…For instance, the overexpression of c-fos in transgenic mice resulted in altered T cell development and impaired B cell function (Ruther et al, 1988). Furthermore, c-fos-v-jun double-transgenic mice showed perturbed B cell development in the bone marrow (Fujita et al, 1993). It follows that the regulated expression of AP-1 factors is required for the ordered process of B lymphoid development and function.…”

Section: Modification Of Nfab In B Lymphocytesmentioning

confidence: 99%

IgM receptor-mediated transactivation of the IgH 3′ enhancer couples a novel Elf-1-AP-1 protein complex to the developmental control of enhancer function.

1995

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B cell development is perturbed in bone marrow from c-fos/v-jun doubly transgenic mice

Cited by 12 publications

References 0 publications

Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells

Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells

Genetic and Metabolic Control of the Mitochondrial Transmembrane Potential and Reactive Oxygen Intermediate Production in HIV Disease

IgM receptor-mediated transactivation of the IgH 3′ enhancer couples a novel Elf-1-AP-1 protein complex to the developmental control of enhancer function.

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