Lineage commitment to a T

Research output: ThesisDoctoral Thesis (compilation)

Abstract

he hematopoietic development is a highly dynamic but tightly regulated process. The flexibility to produce blood cells through more than one route will allow the blood system to respond rapidly in stress situations such as infections. On the other hand, regulation of the blood system is required to prevent blood cells from uncontrolled proliferation that could result in leukemia or bone marrow failure due to depletion of blood cells.
Hematopoietic stem cells are cells that can differentiate to all blood lineages and maintain the whole hematopoietic system throughout a lifetime. This differentiation process through which stem cells generate mature blood cells occurs through different lineage commitment steps. The precise mapping of the lineage commitment events in normal hematopoietic development is essential to understand its regulation and also to unravel the underlying mechanisms in various hematological diseases.
The aim of my thesis has been to study and delineate early lineage commitment processes in the hematopoietic stem cell compartment and in lymphopoiesis with a particular emphasis on T cell development in adult and fetal hematopoiesis using the mouse as a model system. In the thesis I present studies that support an alternative lineage commitment model to the classical and prevailing one for hematopoietic development. In the alternative model hematopoietic stem cells generate progenitors with lymphoid/myeloid (granulocyte/monocyte) and megakaryocyte/erythrocyte/myeloid fates as a first step in their lineage commitment. As the progenitors go through the differentiation to become T cells, they do not commit to a final T cell fate until they have reached and entered their final destination, the thymus. In my studies we demonstrate that the progenitor that initially seeds the thymus during early embryonic development and replenishes the thymus postnatally is more multipotent than previously appreciated. This model has not only identified new and critical commitment steps but also provides a better candidate target cell for the origin of biphenotypic leukemia, which is characterized by lymphoid and myeloid phenotypes.

Details

Authors
  • Sidinh Luc
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • Hematopoietic stem cell, hematopoiesis, lineage commitment, lymphoid-primed multipotent progenitor
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
  • Sten Eirik W Jacobsen, Supervisor
Award date2011 Apr 30
Publisher
  • Lund Stem Cell Center
Print ISBNs978-91-86671-93-8
Publication statusPublished - 2011
Publication categoryResearch

Bibliographic note

Defence details Date: 2011-04-30 Time: 09:00 Place: Segerfalk lecture hall, BMC, Lund External reviewer(s) Name: Manz, Markus Title: Prof Affiliation: Zürich University, Zürich, Switzerland --- 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)

Related research output

Luc, S., Anderson, K., Kharazi, S., Buza-Vidas, N., Charlotta Böiers, Christina Jensen, Ma, Z., Wittmann, L. & Jacobsen, S. E. W., 2008, In : Blood. 111, 7, p. 3424-3434

Research output: Contribution to journalArticle

Månsson, R., Anne Hultquist, Luc, S., Yang, L., Anderson, K., Kharazi, S., Al-Hashmi, S., Liuba, K., Thorén, L., Adolfsson, J., Buza-Vidas, N., Qian, H., Soneji, S., Enver, T., Mikael Sigvardsson & Jacobsen, S. E. W., 2007, In : Immunity. 26, 4, p. 407-419

Research output: Contribution to journalArticle

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