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Core circadian clock transcription factor BMAL1 regulates mammary epithelial cell growth, differentiation, and milk component synthesis
Year:
2021
Source of publication :
PLoS ONE
Authors :
Shamay, Avi
;
.
Volume :
Co-Authors:

Theresa Casey
Aridany Suarez-Trujillo
Shelby Cummings 
Katelyn Huff
Jennifer Crodian
Ketaki Bhide 
Clare Aduwari
Kelsey Teeple 
Avi Shamay
Sameer J Mabjeesh
Phillip San Miguel 
Jyothi Thimmapuram 
Karen Plaut 

Facilitators :
From page:
0
To page:
0
(
Total pages:
1
)
Abstract:

The role the mammary epithelial circadian clock plays in gland development and lactation is unknown. We hypothesized that mammary epithelial clocks function to regulate mammogenesis and lactogenesis, and propose the core clock transcription factor BMAL1:CLOCK regulates genes that control mammary epithelial development and milk synthesis. Our objective was to identify transcriptional targets of BMAL1 in undifferentiated (UNDIFF) and lactogen differentiated (DIFF) mammary epithelial cells (HC11) using ChIP-seq. Ensembl gene IDs with the nearest transcriptional start site to ChIP-seq peaks were explored as potential targets, and represented 846 protein coding genes common to UNDIFF and DIFF cells and 2773 unique to DIFF samples. Genes with overlapping peaks between samples (1343) enriched cell-cell adhesion, membrane transporters and lipid metabolism categories. To functionally verify targets, an HC11 line with Bmal1 gene knocked out (BMAL1-KO) using CRISPR-CAS was created. BMAL1-KO cultures had lower cell densities over an eight-day growth curve, which was associated with increased (p<0.05) levels of reactive oxygen species and lower expression of superoxide dismutase 3 (Sod3). RT-qPCR analysis also found lower expression of the putative targets, prolactin receptor (Prlr), Ppara, and beta-casein (Csn2). Findings support our hypothesis and highlight potential importance of clock in mammary development and substrate transport.

Note:
Related Files :
Mammary epithelial cell
Milk component
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More details
DOI :
10.1371/journal.pone.0248199
Article number:
0
Affiliations:
Database:
PubMed
Publication Type:
article
;
.
Language:
English
Editors' remarks:
ID:
56069
Last updated date:
02/03/2022 17:27
Creation date:
25/08/2021 13:28
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Scientific Publication
Core circadian clock transcription factor BMAL1 regulates mammary epithelial cell growth, differentiation, and milk component synthesis

Theresa Casey
Aridany Suarez-Trujillo
Shelby Cummings 
Katelyn Huff
Jennifer Crodian
Ketaki Bhide 
Clare Aduwari
Kelsey Teeple 
Avi Shamay
Sameer J Mabjeesh
Phillip San Miguel 
Jyothi Thimmapuram 
Karen Plaut 

Core circadian clock transcription factor BMAL1 regulates mammary epithelial cell growth, differentiation, and milk component synthesis

The role the mammary epithelial circadian clock plays in gland development and lactation is unknown. We hypothesized that mammary epithelial clocks function to regulate mammogenesis and lactogenesis, and propose the core clock transcription factor BMAL1:CLOCK regulates genes that control mammary epithelial development and milk synthesis. Our objective was to identify transcriptional targets of BMAL1 in undifferentiated (UNDIFF) and lactogen differentiated (DIFF) mammary epithelial cells (HC11) using ChIP-seq. Ensembl gene IDs with the nearest transcriptional start site to ChIP-seq peaks were explored as potential targets, and represented 846 protein coding genes common to UNDIFF and DIFF cells and 2773 unique to DIFF samples. Genes with overlapping peaks between samples (1343) enriched cell-cell adhesion, membrane transporters and lipid metabolism categories. To functionally verify targets, an HC11 line with Bmal1 gene knocked out (BMAL1-KO) using CRISPR-CAS was created. BMAL1-KO cultures had lower cell densities over an eight-day growth curve, which was associated with increased (p<0.05) levels of reactive oxygen species and lower expression of superoxide dismutase 3 (Sod3). RT-qPCR analysis also found lower expression of the putative targets, prolactin receptor (Prlr), Ppara, and beta-casein (Csn2). Findings support our hypothesis and highlight potential importance of clock in mammary development and substrate transport.

Scientific Publication
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