UTSUGISAWA Taiju    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Associate 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 / Foregin	Foregin
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