Publications by authors named "Farbod Famili"

T cell factor 1 (Tcf1) is the first T cell-specific protein induced by Notch signaling in the thymus, leading to the activation of two major target genes, and . Tcf1 deficiency results in partial arrests in T cell development, high apoptosis, and increased development of B and myeloid cells. Phenotypically, seemingly fully T cell-committed thymocytes with Tcf1 deficiency have promiscuous gene expression and an altered epigenetic profile and can dedifferentiate into more immature thymocytes and non-T cells.

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To advance pre-clinical vascular drug research, assays are needed that closely mimic the process of angiogenesis . Such assays should combine physiological relevant culture conditions with robustness and scalability to enable drug screening. We developed a perfused 3D angiogenesis assay that includes endothelial cells (ECs) from induced pluripotent stem cells (iPSC) and assessed its performance and suitability for anti-angiogenic drug screening.

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T cells develop from hematopoietic stem cells in the specialized microenvironment of the thymus. The main transcriptional players of T-cell differentiation such as Notch, Tcf-1, Gata3 and Bcl11b have been identified, but their role and regulation are not yet completely understood. In humans, functional experiments on T-cell development have traditionally been rather difficult to perform, but novel culture systems and xenograft models have allowed detailed studies on human T-cell development.

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The development of blood and immune cells requires strict control by various signaling pathways in order to regulate self-renewal, differentiation and apoptosis in stem and progenitor cells. Recent evidence indicates critical roles for the canonical and non-canonical Wnt pathways in hematopoiesis. The non-canonical Wnt pathway is important for establishment of cell polarity and cell migration and regulates apoptosis in the thymus.

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The Wnt signaling pathway is essential in the development and homeostasis of blood and immune cells, but its exact role is still controversial and is the subject of intense research. The malignant counterpart of normal hematopoietic cells, leukemic (stem) cells, have hijacked the Wnt pathway for their self-renewal and proliferation. Here we review the multiple ways dysregulated Wnt signaling can contribute to leukemogenesis, both cell autonomously as well as by changes in the microenvironment.

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Article Synopsis
  • Canonical Wnt signaling is essential for the self-renewal of stem cells, but in the blood system, high Wnt signals can reduce their reconstituting ability.
  • Research using Apc mutant alleles demonstrated that elevated Wnt levels in hematopoietic stem cells (HSCs) promote differentiation and decrease proliferation, ultimately leading to a loss of stem cell characteristics.
  • The study sheds light on how APC mutations and Wnt signaling impact HSC biology, which could inform future clinical strategies for stem cell expansion.
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Article Synopsis
  • - Tcf1 is crucial for T-cell development in the thymus, as its absence (Tcf1(-/-) mice) leads to developmental issues and significantly small thymuses, particularly during the transition from double negative to double positive T-cells.
  • - Surprisingly, many Tcf1(-/-) mice develop thymic lymphomas by 16 weeks of age, which are aggressive and characterized by high Wnt signaling activity and expression of Wnt target genes.
  • - The loss of Tcf1 removes its repressive influences on the oncogene Lef1, promoting tumor growth, and its deficiency works alongside Notch1 mutations to increase the risk of thymic lymphomas, establishing Tcf1 as a tumor suppressor
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Hepatic NK cells constitute ≈ 40% of hepatic lymphocytes and are phenotypically and functionally distinct from blood NK cells. Whether hepatic NK cells derive from precursors in the BM or develop locally from hepatic progenitors is still unknown. Here, we identify all five known sequential stages of NK-cell development in the adult human liver and demonstrate that CD34(+) hepatic progenitors can generate functional NK cells.

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