IL-7 receptor signaling is necessary for stage transition in adult B cell development through up-regulation of EBF

Kikuchi, Kazu; Lai, Anne Y.; Hsu, Chia Lin; Kondo, Motonari

doi:10.1084/jem.20050158

Cited by 194 publications

(245 citation statements)

References 32 publications

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“…Recent data have indicated that the main action of IL7 signaling at the CLP stage involves the activation of STAT5 but not AKT-mediated signaling (25,26). In contrast, FLT3 signaling most likely activates the PI(3)K pathway until the FLT3 receptor is suppressed at later developmental stages by PAX5 (26). These latter observations raise the question as to how FOXO1 protein abundance is maintained in the presence of FLT3-mediated signaling.…”

Section: Discussionmentioning

confidence: 53%

“…Thus, we are now faced with the question as to whether IL7-and FLT3-mediated signaling modulates FOXO1 nuclear location and abundance. Recent data have indicated that the main action of IL7 signaling at the CLP stage involves the activation of STAT5 but not AKT-mediated signaling (25,26). In contrast, FLT3 signaling most likely activates the PI(3)K pathway until the FLT3 receptor is suppressed at later developmental stages by PAX5 (26).…”

Section: Discussionmentioning

confidence: 99%

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Positive intergenic feedback circuitry, involving EBF1 and FOXO1, orchestrates B-cell fate

Månsson

Welinder

Åhsberg

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Recent studies have identified a number of transcriptional regulators, including E2A, early B-cell factor 1 (EBF1), FOXO1, and paired box gene 5 (PAX5), that promote early B-cell development. However, how this ensemble of regulators mechanistically promotes B-cell fate remains poorly understood. Here we demonstrate that B-cell development in FOXO1-deficient mice is arrested in the common lymphoid progenitor (CLP) LY6D + cell stage. We demonstrate that this phenotype closely resembles the arrest in B-cell development observed in EBF1-deficient mice. Consistent with these observations, we find that the transcription signatures of FOXO1-and EBF1-deficient LY6D + progenitors are strikingly similar, indicating a common set of target genes. Furthermore, we found that depletion of EBF1 expression in LY6D + CLPs severely affects FOXO1 mRNA abundance, whereas depletion of FOXO1 activity in LY6D + CLPs ablates EBF1 transcript levels. We generated a global regulatory network from EBF1 and FOXO1 genome-wide transcription factor occupancy and transcription signatures derived from EBF1-and FOXO1-deficient CLPs. This analysis reveals that EBF1 and FOXO1 act in a positive feedback circuitry to promote and stabilize specification to the B-cell lineage.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Positive intergenic feedback circuitry, involving EBF1 and FOXO1, orchestrates B-cell fate

Månsson

Welinder

Åhsberg

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…In contrast, the size and cellularity of the spleen were relatively normal. Then we analyzed the subsets of B-cell population as previously described [40], which is characterized by B220 Fig. 2A), and B220 + CD43 − IgM + IgD + (mature B cell, Fraction F in Fig.…”

Section: (C D) (C) Frequencies and (D) Absolute Numbers Of Pro-b (B220mentioning

confidence: 99%

Ablation of Wntless in endosteal niches impairs lymphopoiesis rather than HSCs maintenance

et al. 2015

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Osteoblasts and perivascular stromal cells constitute essential niches for HSC selfrenewal and maintenance in the bone marrow. Wnt signaling is important to maintain HSC integrity. However, the paracrine role of Wnt proteins in osteoblasts-supported HSC maintenance and differentiation remains unclear. Here, we investigated hematopoiesis in mice with Wntless (Wls) deficiency in osteoblasts or Nestin-positive mesenchymal progenitor cells, which presumptively block Wnt secretion in osteoblasts. We detected defective B-cell lymphopoiesis and abnormal T-cell infiltration in the bone marrow of Wls mutant mice. Notably, no impact on HSC frequency and repopulation in the bone marrow was observed with the loss of osteoblastic Wls. Our findings revealed a supportive role of Wnts in osteoblasts-regulated B-cell lymphopoiesis. They also suggest a preferential niche role of osteoblastic Wnts for lymphoid cells rather than HSCs, providing new clues for the molecular nature of distinct niches occupied by different hematopoietic cells.Keywords: B cell r HSC maintenance r Osteoblast r T-cell infiltration r Wntless Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionHSCs that periodically generate all hematopoietic lineages are mostly stored in vascular or endosteal niches in the bone marrow [1]. Vascular niches consist of sinusoidal endothelium cells [2][3][4] whereas endosteal niches are mainly composed of osteoblasts [5,6]. These niche cells are important to regulate HSCs self-renewal and maintenance. Recent evidence also reveals that perivascular Nestin + mesenchymal progenitor cells form a supportive niche for HSCs [3,7,8]. In addition, studies from Dr. Morrison suggest that HSCs mainly reside in the perivascular niches whereas the early lymphoid progenitor cells prefer to locate at endosteal niches [9,10].Correspondence: Dr. Xizhi Guo e-mail: xzguo2005@sjtu.edu.cn; zjyao@sjtu.edu.cnCompelling evidence reveals that Wnt signaling is an important regulator for HSCs integrity and function. Wnt proteins, which consist of 19 members in mammals, could be transduced through canonical or noncanonical signaling pathways [11]. β-Catenin is the key and obligatory mediator of canonical Wnt signaling. Stabilized β-catenin expression expands the pool of HSCs and leads to deficiency in HSCs repopulation capacity [12,13]. Conversely, deletion of β-catenin or Wnt3a leads to defective HSCs long-term maintenance [14,15]. Nevertheless, several lines of evidence also indicate that β-catenin is dispensable for HSCs maintenance [16,17]. On the other hand, inhibition of environmental canonical Wnt signaling in osteoblasts impairs HSCs self-renewal and quiescence [18]. Collectively, canonical Wnt signaling is revealed to * These authors contributed equally to this work. regulate HSCs self-renewal in a dosage-dependent manner [19]. In addition, noncanonical Wnt signaling is also reported to sustain HSCs maintenance and aging [20,21]. Osteoblasts also support B-cell commitment an...

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“…For example, GM-colony-stimulating factor (GM-CSF) was shown to direct macrophage vs. neutrophil outcome in myeloid progenitors by regulating the CCAAT enhancer-binding protein-␣ (C͞EBP␣) and PU.1 expression levels (7). IL-7 was also demonstrated to up-regulate early B cell factor (EBF) expression level in preproB cell and promote transition to proB cell stage during B cell development (8). Nonetheless, it is not clear whether cytokines are involved in determining lymphoid vs. myeloid lineage decision in more primitive progenitors.…”

mentioning

confidence: 99%

Antagonistic effect of CCAAT enhancer-binding protein-α and Pax5 in myeloid or lymphoid lineage choice in common lymphoid progenitors

Hsu

Fleischman

Lai

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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IL-7 receptor signaling is necessary for stage transition in adult B cell development through up-regulation of EBF

Cited by 194 publications

References 32 publications

Positive intergenic feedback circuitry, involving EBF1 and FOXO1, orchestrates B-cell fate

Positive intergenic feedback circuitry, involving EBF1 and FOXO1, orchestrates B-cell fate

Ablation of Wntless in endosteal niches impairs lymphopoiesis rather than HSCs maintenance

Antagonistic effect of CCAAT enhancer-binding protein-α and Pax5 in myeloid or lymphoid lineage choice in common lymphoid progenitors

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