Thread by @dylanrausch

Excited to see my first co-first author paper of my PhD out in @NatureComms! Tweetorial:

In 2016 the Schwartz Lab @UWMDI_UWMed showed a single injection of FGF1 into the brain can permanently revert #Type2Diabetes in @justsaysinmice. We @tunepers lab asked: HOW? (1/9)

With the wet-lab superstar @mariebentsen, we replicated this experiment, but this time, collected hypothalami from these mice at several timepoints following drug injection for #singlecell #transcriptomics with @10xGenomics (2/9)

Our computational analyses found that FGF1 induced massive changes to non-neuronal cells, specifically tanycytes and astrocytes in the first week. Inspired by work from @LiddelowSA on glial reactivity, we asked if FGF1 induced an A2 or A1 state in astrocytes (3/9)

We found that astros initially took on the “helpful“ A2 state, and then morphed into something different... We searched the literature and found that our astrocytes had begun to express genes that are upregulated when astrocytes are co-cultured with neurons @HaselPhilip (4/9)

So we looked to see if our astrocytes were actually interacting with more neurons, and they were! Using EM we saw that astrocytic processes were increased at synaptic boutons and using IHC saw an increase in cellular contacts between Agrp neurons and astrocytes (5/9)

Astrocytes play an important role in regulating neuronal activity, so we took a look at the transcriptomes of the neurons we had sequenced and found that Agrp neurons showed the biggest changes, with strongly reduced expression of Agrp up to 42 days after injection... (6/9)

@mariebentsen tested if that reduction in melanocortin signaling was necessary for FGF1 to work, and it was! Altogether this may suggest that Agrp neuron function is altered as a consequence of FGF1 action on glial cells… (7/9)

And that this may be a key mechanism by which it induces long term diabetes remission.

Read the full paper here: nature.com/articles/s4146…

And check out @marie_bentsen tweetorial for more deets and where we hope to go in the future!

(8/9)

Thanks to all involved incl. @AallingNadia @metteludwig @KLichtenberg2 @pvtodorov and many others not on twitter for the great chats and @cphbiosciphd @Metabolcenter for providing an amazing workplace. Its been an exciting and exhausting, and experience! Ready for the next!