The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Loss of a quiescent niche but not follicle stem cells in the absence of bone morphogenetic protein signaling
Open accessAbstract
During the hair cycle, follicle stem cells (SCs) residing in a specialized niche called the “bulge” undergo bouts of quiescence and activation to cyclically regenerate new hairs. Developmental studies have long implicated the canonical bone morphogenetic protein (BMP) pathway in hair follicle (HF) determination and differentiation, but how BMP signaling functions in the hair follicle SC niche remains unknown. Here, we use loss and gain of function studies to manipulate BMP signaling in the SC niche. We show that when the Bmpr1a gene is conditionally ablated, otherwise quiescent SCs are activated to proliferate, causing an expansion of the niche and loss of slow-cycling cells. Surprisingly, follicle SCs are not lost, however, but rather, they generate long-lived, tumor-like branches that express Sox4, Lhx2, and Sonic Hedgehog but fail to terminally differentiate to make hair. A key component of BMPR1A-deficient SCs is their elevated levels of both Lef1 and β-catenin, which form a bipartite transcription complex required for initiation of the hair cycle. Although β-catenin can be stabilized by Wnt signaling, we show that BMPR1A deficiency enhances β-catenin stabilization in the niche through a pathway involving PTEN inhibition and PI3K/AKT activation. Conversely, sustained BMP signaling in the SC niche blocks activation and promotes premature hair follicle differentiation. Together, these studies reveal the importance of balancing BMP signaling in the SC niche.
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Cites
Identification of the haematopoietic stem cell niche and control of the niche size
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Defining the Epithelial Stem Cell Niche in Skin
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Self-citationMoore, K. A., & Lemischka, I. R. (2006) · Science · doi:10.1126/science.1110542 · Cited by 1,553
Blanpain, C., Lowry, W. E., Geoghegan, A., Polak, L., & Fuchs, E. (2004) · Cell · doi:10.1016/j.cell.2004.08.012 · Cited by 1,428
Self-citationMüller-Röver, S., Foitzik, K., Paus, R., Handjiski, B., van der Veen, C., Eichmüller, S., McKay, I. A., & Stenn, K. S. (2001) · Journal of Investigative Dermatology · doi:10.1046/j.0022-202x.2001.01377.x · Cited by 1,375
β-Catenin Controls Hair Follicle Morphogenesis and Stem Cell Differentiation in the Skin
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Capturing and profiling adult hair follicle stem cells
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De Novo Hair Follicle Morphogenesis and Hair Tumors in Mice Expressing a Truncated β-Catenin in Skin
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Cited by
Massagué, J. (2008) · Cell · doi:10.1016/j.cell.2008.07.001 · Cited by 3,907
Epidermal homeostasis: a balancing act of stem cells in the skin
Blanpain, C., & Fuchs, E. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2636 · Cited by 1,270
Self-citationThe Hair Follicle as a Dynamic Miniorgan
Schneider, M. R., Schmidt-Ullrich, R., & Paus, R. (2009) · Current Biology · doi:10.1016/j.cub.2008.12.005 · Cited by 1,119
Lgr5 marks cycling, yet long-lived, hair follicle stem cells
Jaks, V., Barker, N., Kasper, M., van Es, J. H., Snippert, H. J., Clevers, H., & Toftgård, R. (2008) · Nature Genetics · doi:10.1038/ng.239 · Cited by 966
A Two-Step Mechanism for Stem Cell Activation during Hair Regeneration
Greco, V., Chen, T., Rendl, M., Schober, M., Pasolli, H. A., Stokes, N., dela Cruz-Racelis, J., & Fuchs, E. (2009) · Cell Stem Cell · doi:10.1016/j.stem.2008.12.009 · Cited by 800
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Metadata
- Authors
- Kobielak, K., Stokes, N., de la Cruz, J., Polak, L., & Fuchs, E.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2007-06-12
- Volume
- 104
- Issue
- 24
- Pages
- 10063-10068
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2016450412
- Cited by
- 306
- References
- 42
- FWCI
- 28.04
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Kobielak, K., Stokes, N., de la Cruz, J., Polak, L., & Fuchs, E. (2007). Loss of a quiescent niche but not follicle stem cells in the absence of bone morphogenetic protein signaling. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0703004104
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