Regeneration of immunocompetent B lymphopoiesis from pluripotent stem cells guided by transcription factors
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE180318 | GEO | 2021/12/16
REPOSITORIES: GEO
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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.
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Project description:Mouse B cell precursors from fetal liver and adult bone marrow generate distinctive B cell progeny when transplanted into immunodeficient recipients, supporting a two-pathway model for B lymphopoiesis, fetal “B-1” and adult “B-2”. Recently Lin28b was shown to be important for the switch between fetal and adult pathways; however, neither the mechanism of Lin28b action nor the importance of BCR signaling in this process was addressed. Here we report important advances in our understanding of the regulation of B 1/B-2 development. First, modulation of Let-7 in fetal Pro-B cells is sufficient to alter fetal B-1 development to produce B cells resembling the progeny of adult B-2 development. Second, intact BCR signaling is required for generation of B1a B cells from Lin28b-transduced bone marrow progenitors, supporting a requirement for ligand-dependent selection, as is the case for normal B1a B cells. Third, the VH repertore of Lin28b-induced bone marrow B1a B cells differs from that of normal B1a. Finally we identify the Arid3a transcription factor as a key target of Let-7, whose ectopic expression is sufficient to induce B-1 development in adult Pro-B cells and whose knockdown blocks B-1 development in fetal Pro-B cells. 4 individual sorts of Fr.A and Fr.B/C fractions in bone marrow and fetal liver of BALB/c mice
2015-03-01 | E-GEOD-65533 | biostudies-arrayexpress
Project description:Mouse B cell precursors from fetal liver and adult bone marrow generate distinctive B cell progeny when transplanted into immunodeficient recipients, supporting a two-pathway model for B lymphopoiesis, fetal M-bM-^@M-^\B-1M-bM-^@M-^] and adult M-bM-^@M-^\B-2M-bM-^@M-^]. Recently Lin28b was shown to be important for the switch between fetal and adult pathways; however, neither the mechanism of Lin28b action nor the importance of BCR signaling in this process was addressed. Here we report important advances in our understanding of the regulation of B 1/B-2 development. First, modulation of Let-7 in fetal Pro-B cells is sufficient to alter fetal B-1 development to produce B cells resembling the progeny of adult B-2 development. Second, intact BCR signaling is required for generation of B1a B cells from Lin28b-transduced bone marrow progenitors, supporting a requirement for ligand-dependent selection, as is the case for normal B1a B cells. Third, the VH repertore of Lin28b-induced bone marrow B1a B cells differs from that of normal B1a. Finally we identify the Arid3a transcription factor as a key target of Let-7, whose ectopic expression is sufficient to induce B-1 development in adult Pro-B cells and whose knockdown blocks B-1 development in fetal Pro-B cells. 3 individual sorts of Fr.B/C fractions from bone marrow and fetal liver of BALB/c mice
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Project description:Mouse B cell precursors from fetal liver and adult bone marrow generate distinctive B cell progeny when transplanted into immunodeficient recipients, supporting a two-pathway model for B lymphopoiesis, fetal “B-1” and adult “B-2”. Recently Lin28b was shown to be important for the switch between fetal and adult pathways; however, neither the mechanism of Lin28b action nor the importance of BCR signaling in this process was addressed. Here we report important advances in our understanding of the regulation of B 1/B-2 development. First, modulation of Let-7 in fetal Pro-B cells is sufficient to alter fetal B-1 development to produce B cells resembling the progeny of adult B-2 development. Second, intact BCR signaling is required for generation of B1a B cells from Lin28b-transduced bone marrow progenitors, supporting a requirement for ligand-dependent selection, as is the case for normal B1a B cells. Third, the VH repertore of Lin28b-induced bone marrow B1a B cells differs from that of normal B1a. Finally we identify the Arid3a transcription factor as a key target of Let-7, whose ectopic expression is sufficient to induce B-1 development in adult Pro-B cells and whose knockdown blocks B-1 development in fetal Pro-B cells.
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Project description:Mouse B cell precursors from fetal liver and adult bone marrow generate distinctive B cell progeny when transplanted into immunodeficient recipients, supporting a two-pathway model for B lymphopoiesis, fetal “B-1” and adult “B-2”. Recently Lin28b was shown to be important for the switch between fetal and adult pathways; however, neither the mechanism of Lin28b action nor the importance of BCR signaling in this process was addressed. Here we report important advances in our understanding of the regulation of B 1/B-2 development. First, modulation of Let-7 in fetal Pro-B cells is sufficient to alter fetal B-1 development to produce B cells resembling the progeny of adult B-2 development. Second, intact BCR signaling is required for generation of B1a B cells from Lin28b-transduced bone marrow progenitors, supporting a requirement for ligand-dependent selection, as is the case for normal B1a B cells. Third, the VH repertore of Lin28b-induced bone marrow B1a B cells differs from that of normal B1a. Finally we identify the Arid3a transcription factor as a key target of Let-7, whose ectopic expression is sufficient to induce B-1 development in adult Pro-B cells and whose knockdown blocks B-1 development in fetal Pro-B cells. 2 individual sorts of bone marrow Pro-B cells 4 days after Lin28b retroviral transduction (and 2 sorts of empty vector control) and 2 individual sorts of fetal liver Pro-B cells 4 days after Let-7b retroviral transduction (and 2 sorts of empty vector controls).
2015-03-01 | E-GEOD-65534 | biostudies-arrayexpress
Project description:Mouse B cell precursors from fetal liver and adult bone marrow generate distinctive B cell progeny when transplanted into immunodeficient recipients, supporting a two-pathway model for B lymphopoiesis, fetal “B-1” and adult “B-2”. Recently Lin28b was shown to be important for the switch between fetal and adult pathways; however, neither the mechanism of Lin28b action nor the importance of BCR signaling in this process was addressed. Here we report important advances in our understanding of the regulation of B 1/B-2 development. First, modulation of Let-7 in fetal Pro-B cells is sufficient to alter fetal B-1 development to produce B cells resembling the progeny of adult B-2 development. Second, intact BCR signaling is required for generation of B1a B cells from Lin28b-transduced bone marrow progenitors, supporting a requirement for ligand-dependent selection, as is the case for normal B1a B cells. Third, the VH repertore of Lin28b-induced bone marrow B1a B cells differs from that of normal B1a. Finally we identify the Arid3a transcription factor as a key target of Let-7, whose ectopic expression is sufficient to induce B-1 development in adult Pro-B cells and whose knockdown blocks B-1 development in fetal Pro-B cells.
2015-03-01 | GSE65533 | GEO
Project description:Mouse B cell precursors from fetal liver and adult bone marrow generate distinctive B cell progeny when transplanted into immunodeficient recipients, supporting a two-pathway model for B lymphopoiesis, fetal “B-1” and adult “B-2”. Recently Lin28b was shown to be important for the switch between fetal and adult pathways; however, neither the mechanism of Lin28b action nor the importance of BCR signaling in this process was addressed. Here we report important advances in our understanding of the regulation of B 1/B-2 development. First, modulation of Let-7 in fetal Pro-B cells is sufficient to alter fetal B-1 development to produce B cells resembling the progeny of adult B-2 development. Second, intact BCR signaling is required for generation of B1a B cells from Lin28b-transduced bone marrow progenitors, supporting a requirement for ligand-dependent selection, as is the case for normal B1a B cells. Third, the VH repertore of Lin28b-induced bone marrow B1a B cells differs from that of normal B1a. Finally we identify the Arid3a transcription factor as a key target of Let-7, whose ectopic expression is sufficient to induce B-1 development in adult Pro-B cells and whose knockdown blocks B-1 development in fetal Pro-B cells.
2015-03-01 | GSE65534 | GEO
Project description:Immature B cells in spleens of mouse and human differentiate into at least two subsets of mature B cells, the follicular (FO) B cells and the marginal zone (MZ) B cells, but functions, maturation and other properties of these cells are largely unknown. To solve these questions, in this study, we performed transcriptome analyses of FO and MZ B cells sorted from spleens of normal unimmunized mice using gene chips. By comparison of gene expression profiles between FO and MZ B cells, we identified 1226 genes that are expressed higher in FO B cells than in MZ B cells. On the other hand, 1734 genes were found to be expressed higher in MZ B cells than in FO B cells. We noticed that some of differentially expressed genes have been reportedly characterized in FO and MZ B cells, suggesting the reliability of the analysis. By using FACS analyses, we confirmed that CD36, CD68, and CD49e are expressed on MZ B-cells but not on FO B-cells. These results revealed new phenotypic and functional properties of FO and MZ B cells, and set a molecular basis for further studying differentiation and functions of these mature B cells. Keywords: Comparison of gene expression profiles between mouse follicular and marginal zone B-cells
2006-04-21 | GSE3599 | GEO
Project description:Immature B cells in spleens of mouse and human differentiate into at least two subsets of mature B cells, the follicular (FO) B cells and the marginal zone (MZ) B cells, but functions, maturation and other properties of these cells are largely unknown. To solve these questions, in this study, we performed transcriptome analyses of FO and MZ B cells sorted from spleens of normal unimmunized mice using gene chips. By comparison of gene expression profiles between FO and MZ B cells, we identified 1226 genes that are expressed higher in FO B cells than in MZ B cells. On the other hand, 1734 genes were found to be expressed higher in MZ B cells than in FO B cells. We noticed that some of differentially expressed genes have been reportedly characterized in FO and MZ B cells, suggesting the reliability of the analysis. By using FACS analyses, we confirmed that CD36, CD68, and CD49e are expressed on MZ B-cells but not on FO B-cells. These results revealed new phenotypic and functional properties of FO and MZ B cells, and set a molecular basis for further studying differentiation and functions of these mature B cells. Experiment Overall Design: one follicular B cells replicate and one marginal zone B cells replicate were analyzed.
2008-06-12 | E-GEOD-3599 | biostudies-arrayexpress
Project description:The generation of marginal zone (MZ) B cells is a Notch2 dependent process. We observed that transdifferentiation of follicular (FO) B cells to an MZ-like phenotype is dependent on a lymphopenic environment. We therefore adoptively transftered congenically marked SJL.C20 (CD45.1) mature naive FO B cells into either lymphopenic Rag2-/- or intact C57BL6 (CD45.2) recipient mice and recovered and double sorted intermediate phenotype (MZ-FO) donor B cells at day 4 post transfer from Rag2-/- recipients or both MZ and FO phenotype donor B cells at day 8 post transfer from both recipient groups and performed RNA sequencing.
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