Genetic networks dictating early lymphoid lineage decision events
(2005)- Abstract
- Differentiation from hematopoietic stem cells to mature blood cells of different lineages is a continuous process that requires the coordinated activity of several stage and lineage specific transcription factors. These factors act in a transcriptional hierarchy and also in a combinatorial manner to establish the expression of the genes that comprise a specific differentiation program. The progression of hematopoietic progenitors to the earliest committed B cells is highly dependent of the transcription factor Early B-cell Factor (EBF). In the absence of this factor, B-cell development is arrested at the earliest pre-pro-B-cell stage, while all the other blood cell lineages appear to develop normally. To gain further insight in how... (More)
- Differentiation from hematopoietic stem cells to mature blood cells of different lineages is a continuous process that requires the coordinated activity of several stage and lineage specific transcription factors. These factors act in a transcriptional hierarchy and also in a combinatorial manner to establish the expression of the genes that comprise a specific differentiation program. The progression of hematopoietic progenitors to the earliest committed B cells is highly dependent of the transcription factor Early B-cell Factor (EBF). In the absence of this factor, B-cell development is arrested at the earliest pre-pro-B-cell stage, while all the other blood cell lineages appear to develop normally. To gain further insight in how B-lineage commitment is achieved we have investigated control elements and factors affecting the expression and functional activity of EBF. The identification and cloning of a promoter region flanking the EBF gene revealed that EBF is controlled by auto-regulation and provided additional support for the existence of a transcription factor hierarchy in early B cell development. We have also examined how signaling through the surface receptor Notch affects EBF activity. It is well established that Notch signaling is involved in early lineage decision events, promoting T- on behalf of B-cell differentiation. One important property of Notch in this course of events seems to be its ability to perturb the functional activity of EBF. Moreover, Notch signaling has the capacity to alter fate of already committed B-cells towards T-lineage, even though this feature is rare and only observed in the earliest pre-pro-B cells. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/545292
- author
- Smith, Emma LU
- supervisor
- opponent
-
- Dr. Kee, Barbara, Department of Pathology, University of Chicago
- organization
- publishing date
- 2005
- type
- Thesis
- publication status
- published
- subject
- keywords
- Hematologi, extracellular fluids, Haematology, hematopoiesis, B-cell development, transcription, Notch, EBF, extracellulära vätskor
- publisher
- Hematopoietic Stem Cell Lab Klinikgatan 26, BMC B12 221 84 LUND
- defense location
- Segerfalksalen, Wallenberg Neurocentrum,Sölvegatan 17, Lund
- defense date
- 2005-10-01 10:00:00
- ISBN
- 91-85439-74-6
- language
- English
- LU publication?
- yes
- additional info
- Emma Smith. 2002. Cloning and characterization of a promoter flanking the Early B Cell Factor (EBF) gene indicates roles for E-proteins and autoregulation in the control of EBF expression. The Journal of Immunology, vol 1 pp 261-270. Hematopoietic Stem Cell Laboratory Klinikgatan 26, BMC B12 221 84 LundEmma Smith. 2005. Inhibition of EBF function by active nocth signaling reveals a novel regulatory pathway in early B-cell development. Blood, Hematopoietic Stem Cell Laboratory Klinikgatan 26, BMC B12 221 84 Lund (inpress)Emma Smith. . Notch activation promotes conversion of B cell to T cell fatre at the earliest stages of B cell committed progenitors (manuscript)The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Hematopoietic Stem Cell Laboratory (013022012)
- id
- 970b8a25-7ba0-4da4-bb4a-ef717b1ea763 (old id 545292)
- date added to LUP
- 2016-04-01 16:32:49
- date last changed
- 2018-11-21 20:42:16
@phdthesis{970b8a25-7ba0-4da4-bb4a-ef717b1ea763, abstract = {{Differentiation from hematopoietic stem cells to mature blood cells of different lineages is a continuous process that requires the coordinated activity of several stage and lineage specific transcription factors. These factors act in a transcriptional hierarchy and also in a combinatorial manner to establish the expression of the genes that comprise a specific differentiation program. The progression of hematopoietic progenitors to the earliest committed B cells is highly dependent of the transcription factor Early B-cell Factor (EBF). In the absence of this factor, B-cell development is arrested at the earliest pre-pro-B-cell stage, while all the other blood cell lineages appear to develop normally. To gain further insight in how B-lineage commitment is achieved we have investigated control elements and factors affecting the expression and functional activity of EBF. The identification and cloning of a promoter region flanking the EBF gene revealed that EBF is controlled by auto-regulation and provided additional support for the existence of a transcription factor hierarchy in early B cell development. We have also examined how signaling through the surface receptor Notch affects EBF activity. It is well established that Notch signaling is involved in early lineage decision events, promoting T- on behalf of B-cell differentiation. One important property of Notch in this course of events seems to be its ability to perturb the functional activity of EBF. Moreover, Notch signaling has the capacity to alter fate of already committed B-cells towards T-lineage, even though this feature is rare and only observed in the earliest pre-pro-B cells.}}, author = {{Smith, Emma}}, isbn = {{91-85439-74-6}}, keywords = {{Hematologi; extracellular fluids; Haematology; hematopoiesis; B-cell development; transcription; Notch; EBF; extracellulära vätskor}}, language = {{eng}}, publisher = {{Hematopoietic Stem Cell Lab Klinikgatan 26, BMC B12 221 84 LUND}}, school = {{Lund University}}, title = {{Genetic networks dictating early lymphoid lineage decision events}}, year = {{2005}}, }