PMID- 37382162
OWN - NLM
STAT- MEDLINE
DCOM- 20231115
LR  - 20240218
IS  - 1531-4995 (Electronic)
IS  - 0023-852X (Print)
IS  - 0023-852X (Linking)
VI  - 133
IP  - 12
DP  - 2023 Dec
TI  - Localizing Hormone Receptor Expression to Cellular Compartments in Idiopathic 
      Subglottic Stenosis.
PG  - 3506-3511
LID - 10.1002/lary.30856 [doi]
AB  - OBJECTIVES: Idiopathic subglottic stenosis (iSGS) is an unexplained progressive 
      fibrosis of the upper airway. iSGS almost exclusively affects women; as a result, 
      female hormones (estrogen and progesterone) have been proposed to participate in 
      the pathogenesis of iSGS. Our aim was to localize cell-specific gene expression 
      of estrogen receptors (ESR1 and ESR2) and progesterone receptor (PGR) using an 
      established iSGS single-cell RNA sequencing (scRNAseq) cell atlas. STUDY DESIGN: 
      Ex vivo molecular study of airway scar and healthy mucosa from iSGS patients. 
      METHODS: An established scRNAseq atlas consisting of 25,974 individually 
      sequenced cells from subglottic scar (n = 7) or matched unaffected mucosa (n = 3) 
      in iSGS patients was interrogated for RNA expression of ESR1, ESR2, and PGR. 
      Results were quantified and compared across cell subsets, then visualized using 
      Uniform Manifold Approximation and Projection (UMAP). Confirmatory protein 
      assessment of endocrine receptors in fibroblasts from iSGS patients (n = 5) was 
      performed via flow cytometry. RESULTS: The proximal airway mucosa in iSGS 
      patients demonstrates differential expression of endocrine receptors (ESR1, ESR2, 
      PGR). Within airway scar, endocrine receptors are primarily expressed by 
      fibroblasts, immune cells, and endothelial cells. Fibroblasts show strong ESR1 
      and PGR expression, while immune cells possess RNA for both ESR1 and ESR2. 
      Endothelial cells predominantly express ESR2. Epithelial cells in unaffected 
      mucosa express all three receptors, which are all reduced in airway scar. 
      CONCLUSIONS: scRNAseq data localized endocrine receptor expression to specific 
      cell subsets. These results provide the foundation for future work interrogating 
      how hormone-dependent mechanisms promote, sustain, or participate in iSGS disease 
      pathogenesis. LEVEL OF EVIDENCE: NA; Basic science Laryngoscope, 133:3506-3511, 
      2023.
CI  - (c) 2023 The American Laryngological, Rhinological and Otological Society, Inc.
FAU - Talatala, Edward Ryan R
AU  - Talatala ERR
AD  - Department of Otolaryngology-Head & Neck Surgery, Vanderbilt University Medical 
      Center, Nashville, Tennessee, USA.
FAU - Clark, Evan
AU  - Clark E
AUID- ORCID: 0000-0002-4951-2627
AD  - Department of Otolaryngology-Head & Neck Surgery, Vanderbilt University Medical 
      Center, Nashville, Tennessee, USA.
FAU - Ye, Wenda
AU  - Ye W
AD  - Department of Otolaryngology-Head & Neck Surgery, Vanderbilt University Medical 
      Center, Nashville, Tennessee, USA.
FAU - Davis, Ruth J
AU  - Davis RJ
AD  - Department of Otolaryngology-Head & Neck Surgery, Vanderbilt University Medical 
      Center, Nashville, Tennessee, USA.
FAU - Hillel, Alexander T
AU  - Hillel AT
AUID- ORCID: 0000-0001-8471-5449
AD  - Department of Otolaryngology-Head & Neck Surgery, Johns Hopkins University School 
      of Medicine, Baltimore, Maryland, USA.
FAU - Collins, Samuel L
AU  - Collins SL
AD  - Department of Otolaryngology-Head & Neck Surgery, Johns Hopkins University School 
      of Medicine, Baltimore, Maryland, USA.
FAU - Ramirez-Solano, Marisol
AU  - Ramirez-Solano M
AD  - Department of Biostatistics, Vanderbilt University Medical Center, Nashville, 
      Tennessee, USA.
FAU - Sheng, Quanhu
AU  - Sheng Q
AD  - Department of Biostatistics, Vanderbilt University Medical Center, Nashville, 
      Tennessee, USA.
FAU - Gelbard, Alexander
AU  - Gelbard A
AUID- ORCID: 0000-0003-0078-1305
AD  - Department of Otolaryngology-Head & Neck Surgery, Vanderbilt University Medical 
      Center, Nashville, Tennessee, USA.
LA  - eng
GR  - R01 HL146401/HL/NHLBI NIH HHS/United States
GR  - 1409-22214/PCORI/Patient-Centered Outcomes Research Institute/United States
GR  - R01HL146401/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20230629
PL  - United States
TA  - Laryngoscope
JT  - The Laryngoscope
JID - 8607378
RN  - 0 (Estrogens)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Humans
MH  - Female
MH  - *Cicatrix/pathology
MH  - Endothelial Cells/pathology
MH  - Constriction, Pathologic/complications
MH  - *Laryngostenosis/pathology
MH  - Gene Expression
MH  - Estrogens
MH  - RNA
PMC - PMC10755061
MID - NIHMS1914743
OTO - NOTNLM
OT  - estrogen
OT  - iSGS
OT  - idiopathic subglottic stenosis
OT  - progesterone
OT  - single-cell atlas
COIS- Disclosures: The authors report no conflicts of interest.
EDAT- 2023/06/29 13:42
MHDA- 2023/11/15 06:43
PMCR- 2024/12/01
CRDT- 2023/06/29 06:37
PHST- 2023/05/13 00:00 [revised]
PHST- 2023/01/20 00:00 [received]
PHST- 2023/06/15 00:00 [accepted]
PHST- 2024/12/01 00:00 [pmc-release]
PHST- 2023/11/15 06:43 [medline]
PHST- 2023/06/29 13:42 [pubmed]
PHST- 2023/06/29 06:37 [entrez]
AID - 10.1002/lary.30856 [doi]
PST - ppublish
SO  - Laryngoscope. 2023 Dec;133(12):3506-3511. doi: 10.1002/lary.30856. Epub 2023 Jun 
      29.