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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Bhatia, Mickie Scott, Matthew P. Trowbridge, Jennifer J. |
| Description | Author Affiliation: Trowbridge JJ ( Department of Microbiology and Immunology, University of Western Ontario, 1151 Richmond Street, Suite 2, London, ON, Canada N6A 5B8.); |
| Abstract | The signals that control the regenerative ability of hematopoietic stem cells (HSCs) in response to damage are unknown. Here, we demonstrate that downstream activation of the Hedgehog (Hh) signaling pathway induces cycling and expansion of primitive bone marrow hematopoietic cells under homeostatic conditions and during acute regeneration. However, this effect is at the expense of HSC function, because continued Hh activation during regeneration represses expression of specific cell cycle regulators, leading to HSC exhaustion. In vivo treatment with an inhibitor of the Hh pathway rescues these transcriptional and functional defects in HSCs. Our study establishes Hh signaling as a regulator of the HSC cell cycle machinery that balances hematopoietic homeostasis and regeneration in vivo. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 38 |
| Volume Number | 103 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2006-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cell Cycle Proteins Metabolism Cell Cycle Physiology Hedgehog Proteins Hematopoiesis Hematopoietic Stem Cells Signal Transduction Animals Antigens, Ly Genetics Bone Marrow Cells Cytology Cell Differentiation Cell Lineage Gene Expression Profiling Membrane Proteins Mice Mice, Inbred Strains Proto-Oncogene Proteins C-kit Receptors, Cell Surface Regeneration Spleen Transcription Factors Transcription, Genetic Veratrum Alkaloids Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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