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Welinder, Eva
Publications (4 of 4) Show all publications
Åhsberg, J., Ungerbäck, J., Strid, T., Welinder, E., Stjernberg, J., Larsson, M., . . . Sigvardsson, M. (2013). Early B-cell Factor 1 Regulates the Expansion of B-cell Progenitors in a Dose-dependent Manner. Journal of Biological Chemistry, 288(46), 33449-33461
Open this publication in new window or tab >>Early B-cell Factor 1 Regulates the Expansion of B-cell Progenitors in a Dose-dependent Manner
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2013 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 288, no 46, p. 33449-33461Article in journal (Refereed) Published
Abstract [en]

Transcription factor doses are of importance for normal and malignant B-lymphocyte development; however, the understanding of underlying mechanisms and functional consequences of reduced transcription factor levels is limited. We have analyzed progenitor and B-lineage compartments in mice carrying heterozygote mutations in the E2a, Ebf1, or Pax5 gene. Although lymphoid progenitors from Ebf1 or Pax5 heterozygote mice were specified and lineage-restricted in a manner comparable with Wt progenitors, this process was severely impaired in E2a heterozygote mutant mice. This defect was not significantly enhanced upon combined deletion of E2a with Ebf1 or Pax5. Analysis of the pre-B-cell compartment in Ebf1 heterozygote mice revealed a reduction in cell numbers. These cells expressed Pax5 and other B-lineage-associated genes, and global gene expression analysis suggested that the reduction of the pre-B-cell compartment was a result of impaired pre-B-cell expansion. This idea was supported by a reduction in IL2R-expressing late pre-B-cells as well as by cell cycle analysis and by the finding that the complexity of the VDJ rearrangement patterns was comparable in Wt and Ebf1(+/-) pre-B-cells, although the number of progenitors was reduced. Heterozygote deletion of Ebf1 resulted in impaired response to IL7 in vitro and reduced expression levels of pre-BCR on the cell surface, providing possible explanations for the observed stage-specific reduction in cellular expansion. Thus, transcription factor doses are critical for specification as well as expansion of B-lymphoid progenitors, providing increased insight into the molecular regulation of B-cell development.

Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology, 2013
Keywords
Development; Differentiation; Immunology; Lymphocyte; Transcription Factors
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-103303 (URN)10.1074/jbc.M113.506261 (DOI)000328841700057 ()
Available from: 2014-01-17 Created: 2014-01-16 Last updated: 2019-02-11
Tsapogas, P., Zandi, S., Åhsberg, J., Zetterblad, J., Welinder, E., Jönsson, J.-I., . . . Sigvardsson, M. (2011). IL-7 mediates Ebf-1-dependent lineage restriction in early lymphoid progenitors. Blood, 118(5), 1283-1290
Open this publication in new window or tab >>IL-7 mediates Ebf-1-dependent lineage restriction in early lymphoid progenitors
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2011 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 118, no 5, p. 1283-1290Article in journal (Refereed) Published
Abstract [en]

eficiencies in the IL-7 signaling pathway result in severe disruptions of lymphoid development in adult mice. To understand more about how IL-7 deficiency impacts early lymphoid development, we have investigated lineage restriction events within the common lymphoid progenitor (CLP) compartment in IL-7 knockout mice. This revealed that although IL-7 deficiency had a minor impact on the development of LY6D(-) multipotent CLPs, the formation of the lineage restricted LY6D(+) CLP population was dramatically reduced. This was reflected in a low-level transcription of B-lineage genes as well as in a loss of functional B-cell commitment. The few Ly6D(+) CLPs developed in the absence of IL-7 displayed increased lineage plasticity and low expression of Ebf-1. Absence of Ebf-1 could be linked to increased plasticity because even though Ly6D(+) cells develop in Ebf-1-deficient mice, these cells retain both natural killer and dendritic cell potential. This reveals that IL-7 is essential for normal development of Ly6D(+) CLPs and that Ebf-1 is crucial for lineage restriction in early lymphoid progenitors.

Place, publisher, year, edition, pages
American Society of Hematology, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-70104 (URN)10.1182/blood-2011-01-332189 (DOI)000293510000020 ()
Available from: 2011-08-19 Created: 2011-08-19 Last updated: 2017-12-08
Månsson, R., Zandi, S., Welinder, E., Tsapogas, P., Sakaguchi, N., Bryder, D. & Sigvardsson, M. (2010). Single-cell analysis of the common lymphoid progenitor compartment reveals functional and molecular heterogeneity. Blood, 115(13), 2601-2609
Open this publication in new window or tab >>Single-cell analysis of the common lymphoid progenitor compartment reveals functional and molecular heterogeneity
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2010 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 115, no 13, p. 2601-2609Article in journal (Refereed) Published
Abstract [en]

To investigate molecular events involved in the regulation of lymphoid lineage commitment, we crossed lambda 5 reporter transgenic mice to Rag1-GFP knockin mice. This allowed us to subfractionate common lymphoid progenitors and pre-pro-B (fraction A) cells into lambda 5(-)Rag1(low), lambda 5(-)Rag1(high), and lambda 5(+)Rag1(high) cells. Clonal in vitro differentiation analysis demonstrated that Rag1(low) cells gave rise to B/T and NK cells. Rag1(high) cells displayed reduced NK-cell potential with preserved capacity to generate B- and T-lineage cells, whereas the lambda 5(+) cells were B-lineage restricted. Ebf1 and Pax5 expression was largely confined to the Rag1high populations. These cells also expressed a higher level of the surface protein LY6D, providing an additional tool for the analysis of early lymphoid development. These data suggest that the classic common lymphoid progenitor compartment composes a mixture of cells with relatively restricted lineage potentials, thus opening new possibilities to investigate early hematopoiesis.

Place, publisher, year, edition, pages
American Society of Hematology, 2010
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-54870 (URN)10.1182/blood-2009-08-236398 (DOI)000276201000009 ()
Available from: 2010-04-16 Created: 2010-04-16 Last updated: 2017-12-12
Tsapogas, P., Zandi, S., Åhsberg, J., Welinder, E., Månsson, R., Qian, H. & Sigvardsson, M.Functional and molecular analysis of B-lineage commitment suggests an instructive role for Il-7 in the earliest lymphoid restricted cells.
Open this publication in new window or tab >>Functional and molecular analysis of B-lineage commitment suggests an instructive role for Il-7 in the earliest lymphoid restricted cells
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Deficiencies in the Il-7 signaling pathway result in severe disruptions of lymphoid development in adult mice. In order to understand how Il-7 deficiency impacts early lymphoid development we have investigated lineage restriction events within the CLP compartment of Il-7 knock out mice. This revealed that while Il-7 deficiency had a minor impact on the development and functional properties of LY6D- multipotent CLPs, the formation of the lineage restricted LY6D+ CLP population was dramatically reduced. This was reflected in a low level transcription of B-lineage genes as well as in a loss of functional B-cell commitment in developing progenitors. The defect could not be rescued by ectopic expression of Bcl-2 suggesting that the cytokine act in an instructive manner in early lymphoid development. This clarifies the role of Il-7 in early lymphoid development and puts emphasis on the relevance of the recently defined lineage restricted progenitor cells in lymphoid differentiation.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-61589 (URN)
Available from: 2010-11-17 Created: 2010-11-17 Last updated: 2010-11-17
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