UTSUGISAWA Taiju
   Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine
   Position   Assistant Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Smad7 promotes self-renewal of hematopoietic stem cells.
Journal Formal name:Blood
Abbreviation:Blood
ISSN code:00064971/00064971
Domestic / ForeginForegin
Volume, Issue, Page 108(13),pp.4246-54
Author and coauthor Blank Ulrika, Karlsson Goran, Moody Jennifer L, Utsugisawa Taiju, Magnusson Mattias, Singbrant Sofie, Larsson Jonas, Karlsson Stefan
Publication date 2006/12
Summary The Smad-signaling pathway downstream of the transforming growth factor-beta superfamily of ligands is an evolutionarily conserved signaling circuitry with critical functions in a wide variety of biologic processes. To investigate the role of this pathway in the regulation of hematopoietic stem cells (HSCs), we have blocked Smad signaling by retroviral gene transfer of the inhibitory Smad7 to murine HSCs. We report here that the self-renewal capacity of HSCs is promoted in vivo upon blocking of the entire Smad pathway, as shown by both primary and secondary bone marrow (BM) transplantations. Importantly, HSCs overexpressing Smad7 have an unperturbed differentiation capacity as evidenced by normal contribution to both lymphoid and myeloid cell lineages, suggesting that the Smad pathway regulates self-renewal independently of differentiation. Moreover, phosphorylation of Smads was inhibited in response to ligand stimulation in BM cells, thus verifying impairment of the Smad-signaling cascade in Smad7-overexpressing cells. Taken together, these data reveal an important and previously unappreciated role for the Smad-signaling pathway in the regulation of self-renewal of HSCs in vivo.
DOI 10.1182/blood-2006-02-005611
PMID 16917010