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Hematopoietic Stem Cell Quiescence and Long Term Maintenance: Role of SCL/TAL1

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Book cover Tumor Dormancy, Quiescence, and Senescence, Volume 1

Part of the book series: Tumor Dormancy and Cellular Quiescence and Senescence ((DOQU,volume 1))

Abstract

The life-long production of blood cells depends on the maintenance of the hematopoietic stem cell (HSC) pool. The design of quantitative transplantation assays has been instrumental in providing insight into HSC functions, i.e. sustained self-renewal and multipotentiality: competitive transplantation, limiting dilution analysis to estimate stem cell frequency and stem cell activity as well as serial transplantation assays. These assays indicate intrinsic stem cell heterogeneity and reveal the quiescence of adult HSCs with long term reconstituting capacity, contrasting with fetal HSCs that actively proliferate. Importantly, adult HSCs are maintained in quiescence by their interaction with specialized niches in the bone marrow, via cell surface receptors such as KIT, MPL and CXCR4 expressed on HSCs and membrane-bound ligands present on stromal cells. In response to hematopoietic stress, quiescent HSCs transiently switch into active division to produce progenitors and mature blood cells. This regulation of HSC quiescence is critical for the preservation of long-term stem cell functions as shown by genetic studies, which also demonstrated that the process is controlled by a significant number of transcription factors. Among these, the basic helix-loop-helix transcription factor SCL/TAL1 which is essential for the onset of hematopoiesis, has been shown to regulate HSC quiescence and self-renewal, together with its protein partners, E47, GATA2 and LDB1. The SCL complex controls the transcription of genes such as KIT, establishing a functionally important axis in stem cell regulation.

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Acknowledgements

The work was funded by grants from the Canadian Cancer Society Research Institute and the Canadian Institutes of Health Research (Trang Hoang), and in part by a group grant from the Fonds de Recherche Québec-Santé (FRQS) (IRIC infrastructure). S.R.-Sutterlin received a Research Fellowship Award of the Cole Foundation and of the FRQS.We apologize to many of our colleagues for not being able to reference their work due to editorial limitation.

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  1. Institute for Research in Immunology and Cancer, University of Montreal, 6128, Downtown Station, Montreal, Canada

    Shanti Rojas-Sutterlin & Trang Hoang

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  1. Shanti Rojas-Sutterlin
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  2. Trang Hoang
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Correspondence to Trang Hoang .

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    M.A. Hayat

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Rojas-Sutterlin, S., Hoang, T. (2013). Hematopoietic Stem Cell Quiescence and Long Term Maintenance: Role of SCL/TAL1. In: Hayat, M. (eds) Tumor Dormancy, Quiescence, and Senescence, Volume 1. Tumor Dormancy and Cellular Quiescence and Senescence, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5958-9_8

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