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Characterization of Factors Affecting Hormone Signaling in the Human Mammary Gland With Single-Cell Atlases
Characterization of Factors Affecting Hormone Signaling in the Human Mammary Gland With Si...
Characterization of Factors Affecting Hormone Signaling in the Human Mammary Gland With Single-Cell Atlases

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20260202103155
ISBN  
9798280729711
DDC  
610
저자명  
Phong, Kiet Tuan.
서명/저자  
Characterization of Factors Affecting Hormone Signaling in the Human Mammary Gland With Single-Cell Atlases
발행사항  
[Sl] : University of California, San Francisco, 2025
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2025
형태사항  
158 p
주기사항  
Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
주기사항  
Advisor: Gartner, Zev.
학위논문주기  
Thesis (Ph.D.)--University of California, San Francisco, 2025.
초록/해제  
요약The mammary gland is a dynamic organ with complex paracrine signaling downstream of hormone signaling. A history of pregnancy is protective against breast cancer over a lifetime, but this effect is strongest for an early first full birth. I have created a human breast tissue bank with human donor samples from breast reduction surgeries to study the effect of pregnancy on the breast tissue. A single-cell transcriptomic dataset and matched single-nucleus ATAC dataset were generated to describe the changes in the cell state and cell-cell signaling due to parity. The hormone receptor-positive luminal cells play a central role in the response to hormone signaling, and the degree of response is correlated with age and parity. Increasing age decreases the response to hormones, and parity modifies this relationship to suppress hormone response at the younger age. Cell-cell communications between different cell types are also suppressed in the parous mammary gland. There is a significant signature of interferon response the transcriptional state and accessible chromatin sites of the parous hormone receptor- positive luminal cells, as well as a broad inflammatory signal. These findings suggest a potential interaction of interferon response and hormone signaling in the parous breast. Finally, I generated a single-cell transcriptomics dataset to study the effects of testosterone replacement therapy on the breast tissue of transgender men, and found that testosterone suppresses estrogen signaling in these individuals, and thus potentially provides a protective effect against breast cancer.
일반주제명  
Bioengineering
일반주제명  
Cellular biology
일반주제명  
Oncology
일반주제명  
Obstetrics
일반주제명  
Genetics
키워드  
Epigenomics
키워드  
Hormone signaling
키워드  
Mammary gland
키워드  
Single-cell transcriptomics dataset
기타저자  
University of California, San Francisco Bioengineering
기본자료저록  
Dissertations Abstracts International. 86-12B.
전자적 위치 및 접속  
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MARC

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■1001  ▼aPhong,  Kiet  Tuan.▼0(orcid)0000-0002-9273-4276
■24510▼aCharacterization  of  Factors  Affecting  Hormone  Signaling  in  the  Human  Mammary  Gland  With  Single-Cell  Atlases
■260    ▼a[Sl]▼bUniversity  of  California,  San  Francisco▼c2025
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2025
■300    ▼a158  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  86-12,  Section:  B.
■500    ▼aAdvisor:  Gartner,  Zev.
■5021  ▼aThesis  (Ph.D.)--University  of  California,  San  Francisco,  2025.
■520    ▼aThe  mammary  gland  is  a  dynamic  organ  with  complex  paracrine  signaling  downstream  of  hormone  signaling.  A  history  of  pregnancy  is  protective  against  breast  cancer  over  a  lifetime,  but  this  effect  is  strongest  for  an  early  first  full  birth.  I  have  created  a  human  breast  tissue  bank  with  human  donor  samples  from  breast  reduction  surgeries  to  study  the  effect  of  pregnancy  on  the  breast  tissue.  A  single-cell  transcriptomic  dataset  and  matched  single-nucleus  ATAC  dataset  were  generated  to  describe  the  changes  in  the  cell  state  and  cell-cell  signaling  due  to  parity.  The  hormone  receptor-positive  luminal  cells  play  a  central  role  in  the  response  to  hormone  signaling,  and  the  degree  of  response  is  correlated  with  age  and  parity.  Increasing  age  decreases  the  response  to  hormones,  and  parity  modifies  this  relationship  to  suppress  hormone  response  at  the  younger  age.  Cell-cell  communications  between  different  cell  types  are  also  suppressed  in  the  parous  mammary  gland.  There  is  a  significant  signature  of  interferon  response  the  transcriptional  state  and  accessible  chromatin  sites  of  the  parous  hormone  receptor-  positive  luminal  cells,  as  well  as  a  broad  inflammatory  signal.  These  findings  suggest  a  potential  interaction  of  interferon  response  and  hormone  signaling  in  the  parous  breast.  Finally,  I  generated  a  single-cell  transcriptomics  dataset  to  study  the  effects  of  testosterone  replacement  therapy  on  the  breast  tissue  of  transgender  men,  and  found  that  testosterone  suppresses  estrogen  signaling  in  these  individuals,  and  thus  potentially  provides  a  protective  effect  against  breast  cancer.
■590    ▼aSchool  code:  0034.
■650  4▼aBioengineering
■650  4▼aCellular  biology
■650  4▼aOncology
■650  4▼aObstetrics
■650  4▼aGenetics
■653    ▼aEpigenomics
■653    ▼aHormone  signaling
■653    ▼aMammary  gland
■653    ▼aSingle-cell  transcriptomics  dataset
■690    ▼a0202
■690    ▼a0379
■690    ▼a0992
■690    ▼a0369
■690    ▼a0380
■71020▼aUniversity  of  California,  San  Francisco▼bBioengineering.
■7730  ▼tDissertations  Abstracts  International▼g86-12B.
■790    ▼a0034
■791    ▼aPh.D.
■792    ▼a2025
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17357247▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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