Congratulations to mimi on a very nice piece of work.

Here is the link to the bioRxiv paper https://www.biorxiv.org/content/10.1101/754424v1

It is always great when you can recycle existing data. In this case, Mimi analyzed some beautiful data from the Greco lab Mesa et al 2018 link here where they revisit and measure the same epithelial cells on a mouse epithelium for a week. Fantastic data!

tl;dr synopsis: cells exhibit much better size control in vivo than in vitro.

Recent work from many labs has explored size control in animal cells in vitro and concluded that they exhibit an adder, where a constant amount of volume is added in each cell division cycle (Ginzberg, et al., Elife (2018), Cadart, et al., Nat Comm (2018)). However, to date, there are no comparable studies of mammalian cells in vivo so the physiological relevance of adder mechanisms is unclear.

Mimi performed a single cell analysis of cell size control in epidermal stem cells growing and dividing in a living mouse under normal tissue turnover. She quantified the 3D volume growth and cell cycle progression of epidermal stem cells and found that cell growth is coupled to division through a sizer mechanism operating largely in the G1 phase. I.e., regardless of their size at birth, cells transition through G1/S at similar sizes. Thus, while in vitro tissue culture studies identified adder mechanisms, our work demonstrates that sizer mechanisms are important in vivo. Indeed, cells in vivo exhibit a tighter size control than tissue culture cells in vitro.

Posted
AuthorJan Skotheim

Read all about it here https://www.sciencedirect.com/science/article/pii/S1097276519302813?dgcid=author

Ali shows that targeting dCas9 to specific transcription factor binding sites can be used to inhibit those sites function. Basically, dCas9 outcompetes the TF to block binding. This worked in all the cases we looked at and resulted in increased and decreased transcription depending on the site blocked. As a case study, we examined the pluripotency network in embryonic stem cells and found that an Oct4 site on the Nanog promoter drove positive feedback to maintain pluripotency, and that a Nanog site in the Nanog promoter had the opposite effect and provided negative feedback. This method can be used to individually delete links in transcriptional networks to asses their function without deleting the transcription factor hubs. It was a nice collaboration with Marius Wernig (stem cell inst) and Stanley Qi and Antonia Dominguez (bioengineering). Thanks everyone for making this such a fun collaboration.

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Posted
AuthorJan Skotheim

Read all about it here https://www-cell-com.stanford.idm.oclc.org/molecular-cell/fulltext/S1097-2765(19)30224-2

It is a great paper and a great collaboration with the Sage and Rubin labs (thanks to everyone involved for being excellent). But, don’t let the number authors fool you… Ben did a heroic amount and performed a range of complex and different experiments to address this historic problem of how cyclin D finds its main target, the retinoblastoma protein, to inactivate it via phosphorylation (we think).

Posted
AuthorJan Skotheim

Daniel Berensen defended this thesis last Thursday. Congratulations! It is always so nice to see work reach its conclusion and achievements rightly earned and awarded. We also got excellent reviews for his paper which we should turn around in a week or so (a small miracle - much appreciated). Then he will continue the next phase of his education in the MD program at Stanford. We wish him all the best in his future endeavors (just finish those last experiments for the Rb dilution manuscript first).

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Posted
AuthorJan Skotheim