UBXN3B Is Crucial for B Lymphopoiesis
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ABSTRACT:
PROVIDER: PRJNA1100615 | ENA |
REPOSITORIES: ENA
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Project description:UBXN3B Is Crucial for B Lymphopoiesis [scRNA-seq]
| PRJNA1106177 | ENA
Project description:Hematopoiesis is finely regulated to enable timely production of the right numbers and types of immune cells. Herein, we report the crucial function of UBXN3B in B lymphopoiesis. In the inducible global knockout and B cell-specific Ubxn3b knockout model, the terminal B cell number is reduced by > 90% in both Ubxn3b-/- mouse models. Transfer of wildtype bone marrows to irradiated global Ubxn3b-/- restores the B population, while reverse transplantation fails to do so. The deficiency begins from the precursor stage. The B population drops rapidly with significant apoptosis, presents a much higher level of pro-caspase-3 protein following induction of Ubxn3b knockout. RNA-sequencing reveals significantly suppressed cell cycle genes while upregulated TP53 signaling in Ubxn3b-/- B cells. Ubxn3b-/- mice are highly vulnerable to respiratory viruses, with increased lung viral loads and immunopathology, reduced B population and virus-specific IgM/IgG. This study reveals a cell-intrinsic essential role of UBXN3B in B cell survival and UBXN3B as a potential therapeutic target for B-cell related diseases.
2024-06-12 | GSE264055 | GEO
Project description:Hematopoiesis is finely regulated to enable timely production of the right numbers and types of immune cells. Herein, we report the crucial function of UBXN3B in B lymphopoiesis. In the inducible global knockout and B cell-specific Ubxn3b knockout model, the terminal B cell number is reduced by > 90% in both Ubxn3b-/- mouse models. Transfer of wildtype bone marrows to irradiated global Ubxn3b-/- restores the B population, while reverse transplantation fails to do so. The deficiency begins from the precursor stage. The B population drops rapidly with significant apoptosis, presents a much higher level of pro-caspase-3 protein following induction of Ubxn3b knockout. RNA-sequencing reveals significantly suppressed cell cycle genes while upregulated TP53 signaling in Ubxn3b-/- B cells. Ubxn3b-/- mice are highly vulnerable to respiratory viruses, with increased lung viral loads and immunopathology, reduced B population and virus-specific IgM/IgG. This study reveals a cell-intrinsic essential role of UBXN3B in B cell survival and UBXN3B as a potential therapeutic target for B-cell related diseases.
2024-05-31 | GSE266190 | GEO
Project description:Transcription factor (TF) networks determine cell fate in hematopoiesis. However, how TFs cooperate with other regulatory mechanisms to instruct transcription remains poorly understood. We demonstrate in small pre-B cells, that the lineage restricted epigenetic reader BRWD1 closes early development enhancers and opens the enhancers of late B lymphopoiesis to TF binding. BRWD1 differentially regulated over 7000 genes including repressing proliferative and inducing differentiation programs. However, BRWD1 did not regulate expression of transcription factors required for B lymphopoiesis. Hypogammaglobulinemia patients with BRWD1 mutations had B cell transcriptional profiles and enhancer landscapes similar to those observed in Brwd1-/- mice. These data indicate that in both mice and humans, BRWD1 is a master orchestrator of enhancer accessibility that cooperates with TF networks to drive late B cell development.
2018-08-11 | GSE103057 | GEO
Project description:In B lymphopoiesis, activation of the pre-B cell antigen receptor (pre-BCR) is associated with both cell cycle exit and Igk recombination. Yet, how the pre-BCR mediates these functions remains unclear. Herein, we demonstrate that the pre-BCR initiates a feed-forward IRF4-CXC Receptor 4 (CXCR4) amplification loop. ERK activation by CXCR4 then directs the development of small and immature B cells including orchestrating cell cycle exit, pre-BCR repression, Igk recombination and BCR expression. In contrast, escape from IL-7 and pre-BCR expression have only modest effects on B cell developmental transcriptional and epigenetic programs. These data demonstrate a direct and central role for CXCR4 in orchestrating late B cell lymphopoiesis. Furthermore, in the context of previous findings, our data provide a three-receptor system sufficient to recapitulate the essential features of B lymphopoiesis in vitro.
2019-06-18 | GSE129311 | GEO
Project description:We identified that the coordinated expression of exogenous transcription factors(Lhx2, Hoxa9, and Runx1), efficiently guides PSC-derived hematopoietic progenitors (iHPC) preferentially towards B cell lineage commitment, which successfully regenerate B lymphopoiesis in B-cell deficient animals. Of note, the abundancy of in vivo lymphopoiesis includes pro/pre-B progenitors, immature B cells, and all subsets of mature B1a, B1b, FO B and MZ B reconstitution in vivo. We performed single-cell RNA-Seq using the sorted GFP+CD45+ Lin- cells from the bone marrow of recipients at day 7.5 after iHPC transplantation.
2021-12-16 | GSE180319 | GEO
Project description:We identified that the coordinated expression of exogenous transcription factors efficiently guides PSC-derived hematopoietic progenitors (iHPC) preferentially towards B cell lineage commitment, which successfully regenerate B lymphopoiesis in B-cell deficient animals. Of note, the abundancy of in vivo lymphopoiesis includes pro/pre-B progenitors, immature B cells, and all subsets of mature B1a, B1b, FO B and MZ B reconstitution in vivo. We performed BCR deep sequencing using the sorted naive follicular B cells from the spleen of one recipient at week 4 after iHPC transplantation and one C57BL/6 mouse as control.
2021-12-16 | GSE180318 | GEO
Project description:Mir-9-1 controls osteoblastic regulation of lymphopoiesis
| PRJNA998922 | ENA
Project description:BRWD1 orchestrates epigenetic landscape of late B lymphopoiesis
| PRJNA400057 | ENA
Project description:The highly conserved MicroRNA-9 (miR-9) family consists of three members. We discovered that miR-9-1 deletion reduced mature miR-9 expression, causing 43% of the mice to display smaller size and postweaning lethality. MiR-9-1-deficient mice with growth defects experienced severe lymphopenia, but other blood cells were unaffected. The lymphopenia wasn’t due to defects in hematopoietic progenitors, as mutant bone marrow (BM) cells underwent normal lymphopoiesis after transplantation into wild-type recipients. Additionally, miR-9-1-deficient mice exhibited impaired osteoblastic bone formation, as mutant mesenchymal stem cells (MSCs) failed to differentiate into osteoblastic cells (OBs). RNA sequencing revealed reduced expression of master transcription factors for osteoblastic differentiation, Runt-related transcription factor 2 (Runx2) and Osterix (Osx), and genes related to collagen formation, extracellular matrix organization, and cell adhesion, in miR-9-1-deficient MSCs. Follistatin (Fst), an antagonist of bone morphogenetic proteins (BMPs), was found to be a direct target of miR-9-1. Its deficiency led to the up-regulation of Fst, inhibiting BMP signaling in MSCs, and reducing IL-7 and IGF-1. Thus, miR-9-1 controls osteoblastic regulation of lymphopoiesis by targeting the Fst/BMP/Smad signaling axis.
2023-08-31 | GSE239376 | GEO