Genetic networks dictating early lymphoid lineage decision events

TY - THES

T1 - Genetic networks dictating early lymphoid lineage decision events

AU - Smith, Emma

N1 - Defence details Date: 2005-10-01 Time: 10:00 Place: Segerfalksalen, Wallenberg Neurocentrum,Sölvegatan 17, Lund External reviewer(s) Name: Kee, Barbara Title: Dr. Affiliation: Department of Pathology, University of Chicago --- <div class="article_info">Emma Smith. <span class="article_issue_date">2002</span>. <span class="article_title">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.</span> <span class="journal_series_title">The Journal of Immunology</span>, <span class="journal_volume">vol 1</span> <span class="journal_pages">pp 261-270</span>. <span class="journal_distributor">Hematopoietic Stem Cell Laboratory Klinikgatan 26, BMC B12 221 84 Lund</span></div> <div class="article_info">Emma Smith. <span class="article_issue_date">2005</span>. <span class="article_title">Inhibition of EBF function by active nocth signaling reveals a novel regulatory pathway in early B-cell development.</span> <span class="journal_series_title">Blood</span>, <span class="journal_distributor">Hematopoietic Stem Cell Laboratory Klinikgatan 26, BMC B12 221 84 Lund</span> (inpress)</div> <div class="article_info">Emma Smith. <span class="article_issue_date"></span>. <span class="article_title">Notch activation promotes conversion of B cell to T cell fatre at the earliest stages of B cell committed progenitors</span> (manuscript)</div> 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)

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

KW - Hematologi

KW - extracellular fluids

KW - Haematology

KW - hematopoiesis

KW - B-cell development

KW - transcription

KW - Notch

KW - EBF

KW - extracellulära vätskor

M3 - Doctoral Thesis (compilation)

SN - 91-85439-74-6

PB - Hematopoietic Stem Cell Lab Klinikgatan 26, BMC B12 221 84 LUND

ER -