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MACROENVIRONMENTAL REGULATION OF HAIR FOLLICLE STEM CELLS
by
Damon Nino de la Cruz
___________________________________________________
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(PATHOBIOLOGY)
August 2012
Copyright 2012 Damon Nino de la Cruz
Object Description
| Title | Macroenvironmental regulation of hair follicle stem cells |
| Author | de la Cruz, Damon Nino |
| Author email | dndelacr@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Pathobiology |
| School | Keck School of Medicine |
| Date defended/completed | 2012-04-14 |
| Date submitted | 2012-07-23 |
| Date approved | 2012-07-23 |
| Restricted until | 2012-07-23 |
| Date published | 2012-07-23 |
| Advisor (committee chair) | Chuong, Cheng-Ming |
| Advisor (committee member) |
Dubeau, Louis Coetzee, Gerhard (Gerry) A. Widelitz, Randall B. |
| Abstract | The burgeoning field of stem cell research is expanding beyond the initial studies that involved localizing, isolating and culturing of the cells. How stem cell homeostasis is regulated is now the focus of current research. Even more nascent is the idea of how homeostasis is regulated from signals outside the defined stem cell niche or microenvironment. The extra-niche area is defined as the Macroenvironment. This includes adjacent tissue, distant organ systems and even the external environment. To investigate the macroenviroment as a stem cell regulator, hair follicle stem cell interactions with 1)adjacent tissues (subcutaneous adipose tissue), 2)remote signalling (neuroendocrine signalling), and 3)the external environment (circadian rhythms) were studied. Capitalizing on recent work that highlighted inhibitory Bmp2 signalling from the subcutaneous adipose tissue to be in phase with quiescent telogen and non-propogating autonomous anagen portions of the hair cycle we investigate the post-natal development of the dermal fat layer in relation to hair follicle development. During pregnancy in humans and mice modulation to the hair wave, hair cycle and ultimately hair follicle stem cells has been recorded in both classical and current literature yet no studies have been recorded that investigate this phenomena in detail. Using a murine system it is shown show that the hair wave is reset to a telogen resting phase as a consequence of prolactin signalling late in pregnancy and throughout lactation. Additionally, it is observed using in situ hybridization that the prolactin signalling is mediated via the increased expression of prolactin receptors associated with the dermal fat layer and subsequent expression of Bmp2. In the murine model hair grows in a cyclic fashion. Although much of the cycle has been elucidated the source of cycle timing still eludes hair biologist. Using current mouse technologies from the field of circadian rhythms we investigate the possible role of peripheral clocks in the skin by ablating the core component Bmal1 from the circadian clock system in a skin specific knock out model, K14creERtam, Bmal1 mice. These studies have impact on not only the field of hair biology but on a larger scale stem cell research, regenerative medicine and pathologies involved with adipose tissue, hormonal signalling involved with cancers, and circadian rhythms. |
| Keyword | hair follicle; pregnancy; subcutaneous adipose tissue; circadian rhythms |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Contributing entity | University of Southern California |
| Rights | de la Cruz, Damon Nino |
| Physical access | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@lib.usc.edu |
| Archival file | uscthesesreloadpub_Volume4/etd-delaCruzDa-970.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@lib.usc.edu |
| Full text | MACROENVIRONMENTAL REGULATION OF HAIR FOLLICLE STEM CELLS by Damon Nino de la Cruz ___________________________________________________ A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (PATHOBIOLOGY) August 2012 Copyright 2012 Damon Nino de la Cruz |
