Citation

A Two Step Mechanism for Stem Cell Activation During Hair Regeneration

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Abstract:

The stem cells of the adult hair follicle are thought to reside in a niche, referred to as the bulge. The adult bulge epithelial stem cells undergo cycles of activation and rest to sustain hair follicle regeneration throughout life. Several lines of evidences revealed a crucial role for the mesenchymal dermal papilla (DP) cells in triggering a new hair follicle growth at each cycle. However, how these transitions between rest and growth phases are orchestrated remains unknown. In particular how the stem cell niche avoids stem cell depletion and which pathways are required for this process are still not well understood.
To understand better this process, we have examined in detail the phase between hair follicle rest and growth initiation, focusing on the spatial relationship between the epithelial stem cells and the mesenchymal dermal papilla. During the resting phase, the hair germ separates the DP from the bulge stem cells. Hair germ cells, derived from bulge cells, become responsive sooner than the bulge, proliferating and contributing to the early stages of hair follicle regeneration. Moreover when purified and cultured, hair germ cells proliferate more rapidly than bulge cells but fail in long-term transfer.
Molecular analyses show that the hair germ cells downregulate bulge SC markers NFATc1, Tcf3, Sox9 and Lgr5, but they more closely resemble the activated bulge than the transit-amplifying (matrix) cells. Transcriptional profiling reveals precocious activity of both hair germ and DP at the end of the resting phase, accompanied by Wnt MAPKinase signaling in the hair germ and elevated FGFs and BMP inhibitors in DP. We show that FGFs participate with BMP inhibitors in exerting selective and potent stimuli to the hair germ both in vivo and in vitro.
These findings provide for the first time a mechanism by which the balance between stem cell slow cycling and active organ growth can be reconciled. Our findings show how an efficient growth can be achieved by organizing the stem cell niche in two groups. One group, the hair germ, with the ability to respond quickly to growth promoting signals, which provides the first cellular body giving rise to the new organ. The other composed by the majority of stem cells which is the real engine contributing later to the organ growth.
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Association:
Name: Connecticut's Stem Cell Research International Symposium
URL:
http://stemconn.org


Citation:
URL: http://citation.allacademic.com/meta/p306536_index.html
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MLA Citation:

Greco, Valentina. "A Two Step Mechanism for Stem Cell Activation During Hair Regeneration" Paper presented at the annual meeting of the Connecticut's Stem Cell Research International Symposium, Omni Hotel, New Haven, CT, Mar 23, 2009 <Not Available>. 2014-11-29 <http://citation.allacademic.com/meta/p306536_index.html>

APA Citation:

Greco, V. , 2009-03-23 "A Two Step Mechanism for Stem Cell Activation During Hair Regeneration" Paper presented at the annual meeting of the Connecticut's Stem Cell Research International Symposium, Omni Hotel, New Haven, CT <Not Available>. 2014-11-29 from http://citation.allacademic.com/meta/p306536_index.html

Publication Type: Poster
Review Method: Peer Reviewed
Abstract: The stem cells of the adult hair follicle are thought to reside in a niche, referred to as the bulge. The adult bulge epithelial stem cells undergo cycles of activation and rest to sustain hair follicle regeneration throughout life. Several lines of evidences revealed a crucial role for the mesenchymal dermal papilla (DP) cells in triggering a new hair follicle growth at each cycle. However, how these transitions between rest and growth phases are orchestrated remains unknown. In particular how the stem cell niche avoids stem cell depletion and which pathways are required for this process are still not well understood.
To understand better this process, we have examined in detail the phase between hair follicle rest and growth initiation, focusing on the spatial relationship between the epithelial stem cells and the mesenchymal dermal papilla. During the resting phase, the hair germ separates the DP from the bulge stem cells. Hair germ cells, derived from bulge cells, become responsive sooner than the bulge, proliferating and contributing to the early stages of hair follicle regeneration. Moreover when purified and cultured, hair germ cells proliferate more rapidly than bulge cells but fail in long-term transfer.
Molecular analyses show that the hair germ cells downregulate bulge SC markers NFATc1, Tcf3, Sox9 and Lgr5, but they more closely resemble the activated bulge than the transit-amplifying (matrix) cells. Transcriptional profiling reveals precocious activity of both hair germ and DP at the end of the resting phase, accompanied by Wnt MAPKinase signaling in the hair germ and elevated FGFs and BMP inhibitors in DP. We show that FGFs participate with BMP inhibitors in exerting selective and potent stimuli to the hair germ both in vivo and in vitro.
These findings provide for the first time a mechanism by which the balance between stem cell slow cycling and active organ growth can be reconciled. Our findings show how an efficient growth can be achieved by organizing the stem cell niche in two groups. One group, the hair germ, with the ability to respond quickly to growth promoting signals, which provides the first cellular body giving rise to the new organ. The other composed by the majority of stem cells which is the real engine contributing later to the organ growth.


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