Ian Macara, Ph.D.
Louise B. McGavock Professor, and Chair

Dept. of Cell and Developmental Biology

Vanderbilt University School of Medicine

 

 

Keywords: VCSCB SPRING seminar

Record History
Added on August 12, 2021 at 10:56 AM by Uttz, Pam
Modified on March 29, 2022 at 3:03 PM by Uttz, Pam
Shared with (contributions)
Public: SPRING Meeting

Meeting Details

Start Date / Time January 26, 2022 at 9:00 AM
End Date / Time January 26, 2022 at 10:00 AM
Duration 1 hour(s)
Location Zoom
Presenter Name Ian Macara, Ph.D.
Presentation Title “A Self-Limiting Circuit Regulates Mammary Cap Cell Plasticity”
Status This meeting has already occurred

Meeting Agenda/Notes

Membership Renewal talk
The organization and maintenance of complex tissues requires emergent properties driven by self-organizing and self-limiting cell-cell interactions.  We examined these interactions in the mouse mammary gland.  Luminal and myoepithelial subpopulations of the postnatal mammary gland arise from unipotent progenitors, but the destiny of cap cells, which enclose terminal end buds (TEB) in pubertal mice, has remained controversial.  Using a transgenic strain that specifically marks cap cells, we found ~50% of these cells undergo divisions perpendicular to the TEB surface, suggesting they might contribute to the underlying luminal cell population. To address their stemness potential we developed a lineage tracing mouse driven by a cap cell-specific promoter. Induction of tdTomato (tdTom) from this promoter in vivo demonstrated that all cap cell progeny are myoepithelial, with no conversion to the luminal lineage.  However, isolated cap cells in culture generated mixtures of luminal and myoepithelial cells.  Moreover, ablation of luminal cells in vivo using diphtheria toxin triggered repopulation by progeny of tdTom+ cap cells.  A signaling inhibitor screen identified the TGFb pathway as a potential regulator of multipotency. TGFbR inhibitors or gene deletion blocked conversion to the luminal lineage, consistent with an autocrine loop in which cap cells secrete TGFb to activate the receptor and promote luminal lineage specification.  Notably, in vitro transdifferentiation of cap cells was blocked by co-culture with luminal cells.  Overall, these data reveal a self-limiting cell circuit through which mammary luminal cells suppress cap cell conversion to the luminal lineage.

Attachment

Document SPRING_Meeting_1.26.22.pdf - Added on March 29, 2022 at 3:00 PM by Pam Uttz