The role of Smad signaling in hematopoiesis.
The TGF-beta family of ligands, including TGF-beta, bone morphogenetic protein (BMP) and activin, signal through Smad pathways to regulate the fate of hematopoietic progenitor and stem cells during development and postnatally. BMP regulates hematopoietic stem cell (HSC) specification during development, while TGF-beta1, 2 and 3 are not essential for the generation of HSCs. BMP4 can increase proliferation of human hematopoietic progenitors, while TGF-beta acts as a negative regulator of hematopoietic progenitor and stem cells in vitro. In contrast, TGF-beta signaling deficiency in vivo does not affect proliferation of HSCs and does not affect lineage choice either. Therefore, the outcome of Smad signaling is very context dependent in hematopoiesis and regulation of hematopoietic stem and progenitor cells is more complicated in the bone marrow microenvironment in vivo than is seen in liquid cultures ex vivo. Smad signaling regulates hematopoiesis by crosstalk with other regulatory signals and future research will define in more detail how the various pathways interact and how the knowledge obtained can be used to develop advanced cell therapies.
Larsson
Jonas
J
Molecular Medicine and Gene Therapy, Institute of Laboratory Medicine, The Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, BMC A12, Lund 221 84, Sweden.
Karlsson
Stefan
S
D000818:Animals; D016026:Bone Marrow Transplantation; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins; D015534:Trans-Activators / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D053773:Transforming Growth Factor beta1
C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D051785:Smad Proteins; C508960:TGFB1 protein, human; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1