EMBO/SourceData huggingface dataset:
Figure legend: "(D) Immunofluorescence analysis of young CX3CR1+/GFP and old APPPS1/CX3CR1+/GFP slices freshly cut (0 DIV), cultured alone or in co-culture (10 DIV) and immunostained using GFP (green) shows alterations in microglial morphology of old cells upon culturing. Upper-left panels are enlargements of boxed regions. A GFP antibody was used to amplify the signal of GFP-expressing old microglial cells. Scale bars: 50 µm.(E) Quantitative analysis of amoeboid microglial cells in young CX3CR1+/GFP (white bars) and old APPPS1/CX3CR1+/GFP (green bars) brain slices freshly cut (0 DIV), cultured alone or in co-culture (10 DIV). The values are expressed as percentages of amoeboid microglia from the total number of microglial cells. The values represent mean ± SEM from 3 independent experiments, each experiment including at least 250 cells per condition (*P &lt; 0.05, ***P &lt; 0.001)."
NCBI gene IDs:
"APP: 351
PS1: 5663"
Figure legend: "(A) Old APPPS1 tissue was cultured alone (old alone, white bars) or incubated with conditioned media (CM) collected from young WT slices (old alone + young CM, grey bars). Analysis included co-culture of old APPPS1 and young WT brain slices (old co-culture, black bars) as a positive control and old APPPS1 tissue incubated with conditioned media collected from old APPPS1 slices (old alone + old CM, white squared bars) as a negative control. Quantitative analysis at 7, 11 and 14 DIV reveals increased numbers of core-only plaques upon incubation of the old APPPS1 tissue with conditioned media collected from young WT slices, fully recapitulating core-only plaque numbers observed in the co-culture. The values are expressed as percentages of core-only plaques from the total number of amyloid plaques and represent mean ± SEM from 3 independent experiments, each experiment including at least 2 independent slice culture dishes (n.s.= not significant, **P &lt;0.01, ***P &lt; 0.001)."
NCBI gene IDs:
"APP: 351
PS1: 5663"
Figure legend: "(B) Old APPPS1 tissue was incubated with conditioned media collected from young WT slices previously treated with clodronate (old alone + young CM + Clo, grey bars ) and vehicle control (old alone + young CM + Ctr, white bars). Quantitative analysis at 7, 11 and 14 DIV reveals decreased numbers of core-only plaques upon incubation of the old APPPS1 tissue with conditioned media collected from young WT slices pre-treated with Clo. The values are expressed as percentages of core-only plaques from the total number of amyloid plaques and represent mean ± SEM from 3 independent experiments, each experiment including at least 2 independent slice culture dishes (n.s.= not significant, ***P &lt; 0.001)."
NCBI gene IDs:
"APP: 351
PS1: 5663"
Figure legend: "(C) Old APPPS1 tissue was incubated with conditioned media collected from cultured WT primary microglial cells (old alone + MG CM, grey bar) or with unconditioned slice culture media as a control (old alone + Ctr, white bar). Quantitative analysis of core-only plaques at 14 DIV reveals enhanced amyloid plaque clearance upon incubation of the old APPPS1 tissue with conditioned media collected from cultured primary microglia. The values are expressed as percentages of core-only plaques from the total number of amyloid plaques and represent mean ± SEM from 3 independent experiments, each experiment including 2 independent slice culture dishes (*P &lt; 0.05)."
NCBI gene IDs:
"APP: 351
PS1: 5663"
Figure legend: "(A-F) Immunofluorescence analysis of the old APPPS1 slice (14 DIV) treated with vehicle Ctr in A, anti-inflammatory factors IL-10 and TGF-β in B and C and pro-inflammatory factors IL-6, IL-12/p40 and GM-CSF in D, E and F, respectively and immunostained with CD68 (red) and M3.2 (green). In contrast to increased number of core-only plaques upon GM-CSF treatment, other factors tested did not induce amyloid plaque clearance, resulting in a better preservation of the M3.2 positive halos of Aβ surrounding dense core of amyloid plaques. Scale bar: 50 µm."
NCBI gene IDs:
"APP: 351
PS1: 5663"
Figure legend: "(A) CD68 coverage in the old APPPS1 tissue (14 DIV) treated with GM-CSF and vehicle Ctr. CD68 coverage is increased upon treatment with GM-CSF. The values are normalized to CD68 coverage of the Ctr and represent mean ± SEM from 3 independent experiments, each experiment including 2 independent slice culture dishes (*P &lt; 0.05)."
NCBI gene IDs:
"APP: 351
PS1: 5663"
Figure legend: "(B) Quantitative analysis of core-only plaques in the old APPPS1 tissue (14 DIV) treated with GM-CSF and Ctr reveals an increased number of core-only plaques upon treatment with GM-CSF. The values are expressed as percentages of core-only plaques from the total number of amyloid plaques and represent mean ± SEM from 3 independent experiments, each experiment including 3 independent slice culture dishes (***P &lt; 0.001)."
NCBI gene IDs:
"APP: 351
PS1: 5663"
Figure legend: "(C) CD68 coverage in the old APPPS1 tissue (14 DIV) incubated with conditioned media collected from young WT slices (young CM) or with non-conditioned slice culture media (Ctr). CD68 coverage is increased upon incubation of the APPPS1 tissue with the young CM. The values are normalized to CD68 coverage of the Ctr and represent mean ± SEM from 3 independent experiments, each experiment including 2 independent slice culture dishes (**P &lt; 0.01)."
NCBI gene IDs:
"APP: 351
PS1: 5663"
Figure legend: "(D) Immunofluorescence analysis of the old APPPS1 slice cultured alone (old alone) or in co-culture with young GM-CSF-/- brain slices (old co-culture) at 14 DIV and immunostained with CD68 (red) and M3.2 (green) reveals an increased number of core-only plaques upon co-culturing with young GM-CSF-/- brain slices. Scale bar: 50 µm.(E) Quantitative analysis of core-only plaques in the old APPPS1 slice cultured alone or in co-culture with young GM-CSF-/- brain slices (14 DIV) reveals an increased number of core-only plaques upon co-culturing of old APPPS1 brain slices together with young GM-CSF-/- brain slices. The values are expressed as percentages of core-only plaques from the total number of amyloid plaques. The values represent mean ± SEM from 3 independent experiments, each experiment including 3 independent slice culture dishes (***P &lt; 0.001).(F) CD68 coverage in the old APPPS1 tissue (14 DIV) cultured alone or in co-culture with young GM-CSF-/- brain slices. CD68 coverage is increased upon co-culturing of old APPPS1 brain slices together with young GM-CSF-/- brain slices. The values are normalized to CD68 coverage of the old slice cultured alone and represent mean ± SEM from 3 independent experiments, each experiment including 2 independent slice culture dishes (*P &lt; 0.05)."
NCBI gene IDs:
"APP: 351
GM-CSF: 12981
PS1: 5663"
Figure legend: "(A) Immunofluorescence analysis of the old APPPS1 slice (14 DIV) treated with GM-CSF and vehicle Ctr and immunostained with CD68 (red), cell proliferation marker Ki67 (green) and M3.2 (blue). Scale bar: 50 µm.(B) Quantitative analysis of Ki67 and CD68 double positive microglial cells in the old APPPS1 tissue (14 DIV) treated with GM-CSF and Ctr reveals increased microglial proliferation upon treatment with GM-CSF. The values are expressed as percentages of CD68 and Ki67 double positive microglial cells from the total number of CD68 positive cells and represent mean ± SEM from 2 independent experiments, each experiment including 4 independent slice culture dishes (***P &lt; 0.001)."
NCBI gene IDs:
"APP: 351
PS1: 5663"
Figure legend: "(C) Immunofluorescence analysis of the old APPPS1 tissue cultured alone or in co-culture with young WT brain slices (14 DIV) and immunostained with CD68 (red), Ki67 (green) and M3.2 (blue) Scale bar: 50 µm.(D) Quantitative analysis of Ki67 and CD68 double positive microglial cells in the old APPPS1 tissue cultured alone or in co-culture with young brain slices (14 DIV) reveals increased microglial proliferation upon co-culturing of old and young brain slices. The values are expressed as percentages of CD68 and Ki67 double positive microglial cells from the total number of CD68 positive cells and represent mean ± SEM from 3 independent experiments, each experiment including 2 independent slice culture dishes (**P &lt; 0.01)."
NCBI gene IDs:
"APP: 351
PS1: 5663"
Figure legend: "(E) Old APPPS1 tissue was incubated with conditioned media collected from young WT slices and in addition treated with proliferation inhibitor AraC (young CM + AraC) or vehicle Ctr (young CM + Ctr). Immunofluorescence analysis was performed at 14 DIV using CD68 (red) and M3.2 (green). Scale bar: 50 µm.(F) Quantitative analysis of core-only plaques in the old APPPS1 tissue (14 DIV) incubated with conditioned media from young WT slices and in addition treated with AraC or Ctr reveals a decreased number of core-only plaques upon AraC treatment. The values are expressed as percentages of core-only plaques from the total number of amyloid plaques and represent mean ± SEM from 3 independent experiments, each including 2 independent slice culture dishes (***P &lt; 0.001)."
NCBI gene IDs:
"APP: 351
PS1: 5663"
Figure legend: "Time-course analysis of mouse or NMR fibroblasts after DXR treatment qRT-PCR analysis of the expression of INK4a (F) normalized to ACTB mRNA levels"
NCBI gene IDs:
"INK4a: 
ACTB: 101717255"
Figure legend: "qRT-PCR analysis of the expression of INK4a (J) in shINK4a-transduced NMR fibroblasts at 21 days after DXR treatment."
NCBI gene IDs:
"INK4a: "
Figure legend: "quantification of Annexin V-positive cells (%) (K) in shINK4a-transduced NMR fibroblasts at 21 days after DXR treatment."
NCBI gene IDs:
"INK4a: "
Figure legend: "(B) qRT-PCR analysis of the expression of INK4a at 12 days after INK4a or mock transduction, normalized to ACTB mRNA levels."
NCBI gene IDs:
"ACTB: 11461
INK4a: 12578"
Figure legend: "(C) Cell morphology and SA-β-Gal activity of mouse or NMR fibroblasts 12 days after INK4a transduction. Arrowheads indicate dying cells. ​​The number in the upper left corner indicates Hoechst-positive nuclei. Scale bar, 100 μm."
NCBI gene IDs:
"INK4a: 12578"
Figure legend: "(F) Western blot analysis of RB in mouse or NMR fibroblasts at 12 days after INK4a transduction ﻿(p, phospho-specific antibody). ACTIN was used as a loading control. The arrowhead indicates a non-specific band."
NCBI gene IDs:
"INK4a: 12578"
Figure legend: "(I) SA-β-Gal activity in the adherent living cell population and floating dead cell population in mouse or NMR fibroblast cultures at 12 days after INK4a transduction. Scale bar, 100 μm. (J) Quantification of SA-β-Gal-positive cells in the adherent living cell population and floating dead cell population after the same treatment as in I."
NCBI gene IDs:
"INK4a: 12578"
Figure legend: "(C and D) Quantification of SA-β-Gal-positive cells (%) (C) and Annexin V-positive cells (%) (Annexin V+/PI- as early apoptotic and Annexin V+/PI+ double-positive as late apoptotic) (D) in NMR-fibroblasts transduced with different forms of SV40 Large T antigen (LT, LT∆, and LTK1) and INK4a. OE; overexpression."
NCBI gene IDs:
"INK4a: 
Large T antigen: 29031019
LT: 29031019"
Figure legend: "(F) Quantification of SA-β-Gal-positive cells (%) at 21 days after DXR treatment in NMR-fibroblasts transduced with different forms of SV40 Large T antigen (LT, LT∆, and LTK1). (G) Quantification of Annexin V-positive cells after the same treatment as in F. Annexin V+/PI- cells were counted as early apoptotic cells and Annexin V+/PI- cells as late apoptotic cells."
NCBI gene IDs:
"Large T antigen: 29031019
LT: 29031019"
Figure legend: "(B) Left, representative images of lipid peroxidation (green) staining in NMR fibroblasts at 12 days after INK4a-transduction. Scale bar, 50 μm. Right, quantification of signal intensity of lipid peroxidation staining. Data are expressed as the mean ± SD from n = 3 biological replicates."
NCBI gene IDs:
"INK4a: "
Figure legend: "(C) Quantification of PI-positive cells in NMR fibroblasts treated for 24 h with N-acetyl L-cysteine (NAC), Trolox, or Tempol at 20 days after INK4a transduction (%). Data are expressed as the mean ± SD from n = 6 biological replicates except for Trolox and Tempol (n = 4)."
NCBI gene IDs:
"INK4a: "
Figure legend: "(D) Western blot of monoamine oxidase (MAO)-A and MAO-B in mouse or NMR fibroblasts at 20 days after INK4a transduction. ACTIN was used as a loading control. Numbers below the gel images indicate quantification of MAO-A or -B/ACTIN intensity (n = 3 average)."
NCBI gene IDs:
"INK4a: 12578"
Figure legend: "(B) qRT-PCR analysis of INK4a expression in the skin, muscle, and white adipose tissue (WAT) of 6-week-old mice (young; 6 w), 1-year-old mice (middle-aged; 1 y), 1-year-old NMRs (young; 1 y), and 15-year-old NMRs (middle-aged; 15 y)."
NCBI gene IDs:
"INK4a: 12578"
Figure legend: "Time-course analysis of mice or NMR lungs after Bleo administration: qRT-PCR analysis of the expression of INK4a normalized to ACTB mRNA levels (F)"
NCBI gene IDs:
"ACTB: 11461
INK4a: 12578"
Figure legend: "qRT-PCR analysis of INK4a expression normalized to ACTB mRNA levels (D) in mouse or NMR lungs at 21 days after Bleo administration, with or without Phe."
NCBI gene IDs:
"ACTB: 11461
INK4a: 12578"
Figure legend: "(A) Illustration of the crossing and ageing scheme used to obtain total RNA extracts from fly heads for the transcriptional profiling and all successive qPCR assays. Expression of different Atrophin forms with the GMR driver was induced, owing to a temperature‐sensitive mutant Gal80 repressor. F1 flies were allowed to develop at 18°C; at this temperature the Gal80 repressor keeps transgenes silent. Newly eclosed flies (0-48 h) were collected and killed immediately (0d) or aged for 2 or 14 days at 29°C. This inactivates Gal80 and transgenes are switched on by GMR‐Gal4. This protocol allows comparing siblings that differ exclusively in their age and transgenes expression. Control flies crossed to GMR‐Gal4; UbiGal80ts in all experiments are from the w1118 stock in which all UAS transgenes have been generated."
NCBI gene IDs:
"UAS: 
Gal4: 855828
GMR: 855828
Gal80: 854954
Atrophin: 46156"
Figure legend: "(B) Tangential eye sections of flies representative of all the different populations used in the microarray analysis at all different time points. Weak degeneration is only visible after 14 days with polyQ Atro; in particular with Atro75QN there is an initial loss of photoreceptors (PR, arrow), 30.7% of the ommatidia has lost at least 1 PR, that is only 5.1% of all neuronal PR have been lost at this stage (N=333)."
NCBI gene IDs:
"Atro: 46156"
Figure legend: "(A) Heat maps for three subsets of the pattern clustering analysis generated using the Euclidean Distance metric. Upregulated genes are in red and downregulated genes are in green. The downregulating transcriptional activity increases with time. The main branch in clustering of the different Atro mutants is along time points. See also Supplementary Figure 4."
NCBI gene IDs:
"Atro: 46156"
Figure legend: "(B) qPCR analysis of the enrichment±s.d. of different regions of the ft regulatory elements in ChIP for Atro from BG3neuronal cell extracts. Enrichment is calculated as the percentage of DNAimmunoprecipitated from extracts of cells in which Atro expression has been induced, with respect to the amount immunoprecipitated from uninduced cell extracts according to the (Atro-No Ab)induced/(Atro−No Ab)uninduced formula. The DNA region from IV chromosome has been previously shown not to be immunoprecipitated in ChIP for Atro ( Haecker et al, 2007) and has been used as a negative control."
NCBI gene IDs:
"ft: 33627
Atro: 46156"
Figure legend: "(C) Histograms showing the number of ommatidia with a full complement (7) of PR in flies expressing Atro75QN with the Rhodopsin1 driver in either a control (w1118) or different mutant backgrounds and aged at 29°C for 28 days. Heterozygosis for two independent ft alleles and a sav allele significantly enhances the loss of PR. Mild overexpression of Wts via a GMR-wts transgene, which does not display any strong phenotype per se, significantly suppresses the loss of PR. No interaction was detected in this assay with wtsx1 and ykiB5 alleles in heterozygosity. N=430-963 from at least four eyes."
NCBI gene IDs:
"ft: 33627
GMR: 855828
Atro: 46156
Rhodopsin1: 42367
sav: 252554
Wts: 43651
wts: 43651
yki: 37851"
Figure legend: "(D) Tangential eye sections and histograms showing the degeneration of GMR&gt;Atro75QN, Ubi-Gal80ts flies in combination with different UAS transgenes and aged 14 days as in Figure 1A. UAS-EGFP is used as a negative control. Either Ft or Wts overexpression strongly suppresses loss of PR caused by Atro75QN. Lower panels are provided as examples of quantification. A more modest but still significant rescue is observed by overexpressing a Yki RNAi contruct or Hpo; however, in this case it is to be considered that the overexpression of Hpoper se brings about the loss of at least one PR in ∼5% of ommatidia (data not shown). No effect is detected with overexpression of Sav. Two‐tailed t‐test: *P0.05; **P0.01. The wtsEPG4808 is a previously uncharacterised EP element insertion at the 5′ of the wts gene. Rare homozygous escapers display larger eyes, whereas in combination with GMR-GMR this line gives rise to smaller rough eyes, and, finally, GMR analysis of GMR&gt;wtsEPG4808 indicates a 10‐fold increase in the head content of wts mRNA (data not shown)."
NCBI gene IDs:
"EGFP: 
UAS: 
Ft: 33627
GMR: 855828
Gal80: 854954
Atro: 46156
Hpo: 37247
Sav: 252554
Wts: 43651
wts: 43651
Yki: 37851"
Figure legend: "(A) Tangential eye sections through ftfd clones aged 1, 7 and 14 days, of ftfd,dDGC13 double mutant clones and of ftfd clones in a ykiB5 heterozygous background aged 14 days. Clones are marked by the absence of yellow pigment. Arrows point at degenerating photoreceptors, arrowheads point at intact wt photoreceptors in mosaic ommatidia. The circled ommatidium is genetically wt but non‐autonomously flipped in its polarity and has not degenerated. Lower panels are masks that show clonal borders and quantification of PR number per ommatidia. After 14 days, almost all ftfd cells have degenerated, whereas almost all ftfd,dDGC13 and some ftfd,ykiB5/+ neuronalphotoreceptors have not."
NCBI gene IDs:
"ft: 33627
yki: 37851"
Figure legend: "(B) Histograms showing the quantification of degeneration in ftfd, ftfddDGC13 and ftfdykiB5/+ clones. Loss of ft leads to statistically significant loss of neurons and this is suppressed at 14 days by ykiB5and much more dramatically by dDGC13. ***P0.001, **P0.01; *P0.05 in two‐tailed t‐test."
NCBI gene IDs:
"d: 33245
ft: 33627
yki: 37851"
Figure legend: "(C) Degeneration in mosaic ommatidia in ftfd clones. At this stage of degeneration approximately half of the non‐pigmented (genotypically mutant) PR cells display a degenerative phenotype, whereas virtually all pigmented (genotypically wt) PR cells are normal. χ2‐test: 82.38; P0.001. Total PR N=310 (pigmented) and 327 (not pigmented)."
NCBI gene IDs:
"ft: 33627"
Figure legend: "(D) Tangential eye sections through MARCM clone mutants for ftfd that express either no transgene or an RNAi construct against yki (UAS-ykiIR) with Tub-Gal4 and aged 14 days at 29°C. Because the transgene UAS-ykiIR is on chromosomal arm 2 L, the same as ft, clones generated with this system carry two copies of UAS-ykiIR and therefore downregulate yki very effectively. No other cell outside the clones expresses the construct and is therefore wt for yki. Mask panel is presented on the right of each section. A quantification of photoreceptor numbers (far right) displays a very significant increase in the number of wt ommatidia (N=210 and 219 from four eyes). ***P0.001 in two‐tailed t‐test. If all classes of ommatidia are considered, χ2‐test=232.30; P0.001 for 3 degrees of freedom."
NCBI gene IDs:
"UAS: 
ft: 33627
Gal4: 855828
Tub: 40554
yki: 37851"
Figure legend: "(A) Tangential eye sections through wtsX1 mutant fly eyes. In clones for the null wtsX1 allele, degeneration inside the clones is at severe stages at 14 days."
NCBI gene IDs:
"wts: 43651"
Figure legend: "(B) Tangential eye sections through sav3 clones. In sav3 after enclosure many photoreceptors are intact but after 14 days at 29°C most sav mutant photoreceptors have degenerated."
NCBI gene IDs:
"sav: 252554"
Figure legend: "(C) Histograms showing the quantification of ommatidia with the full complement of photoreceptors in hpo, wts and sav mutant clones. The progression of loss of photoreceptors is evident and statistically significant in all cases. Mutants for hpoBF33 do not survive for 14 days at 29oC and corresponding sections are shown in Supplementary Figure 12. N=195-268. ***P0.001, **P0.01; *P0.05 in two‐tailed t‐test."
NCBI gene IDs:
"hpo: 37247
sav: 252554
wts: 43651"
Figure legend: "(A) Regression analysis of the overgrowth versus the neurodegeneration observed in loss of function mutants (left) and overexpression of transgenes (right). Overgrowth quantification is shown in Supplementary Figure 14. For loss of function mutant, the neurodegeneration was quantified at 14 days in clones (as shown in Figures 4 and 5). For UAS‐overexpression transgenes neurodegeneration was quantified at 14 days when expressed with GMRGal4; UbiGal80ts. For CycD+Cdk4, these specific data are missing and have not been plotted; however, Supplementary Figure 13 shows that these mutants do not cause neurodegeneration in a different setup in which they are expressed during both development and adult life. In both cases the regression coefficient r2 is extremely low (0.21 and 0.03), indicating an absence of correlation between the two processes."
NCBI gene IDs:
"UAS: "
Figure legend: "(B) Tangential eye sections through the eyes of flies expressing with GMR-Gal4, Ubi-Gal80ts either UAS-EGFP or UAS-Yki or UAS-YkiS111A,S168A,S250A and aged 1 or 28 days. Arrows point at missing or degenerated photoreceptors. The UAS-YkiS111A,S168A,S250A is so effective that even the very low expression leaking out with this system is enough to affect development and generate mild eye roughness and overproliferation of lattice cells. Histograms showing the quantification of cell loss in eyes shown in A and also eyes from flies aged at the intermediate 14‐day stage. Mild but significant degeneration is observed for both Yki forms, with respect to the negative control; however, no statistical difference is observed between the two Yki proteins that have dramatically different effects on overgrowth. ***P0.001, **P0.01; *P0.05 in two‐tailed t‐test."
NCBI gene IDs:
"EGFP: 
UAS: 
Gal4: 855828
GMR: 855828
Gal80: 854954
Yki: 37851"
Figure legend: "Neurodegeneration by polyQ Atro partially requires dachs. Tangential eye sections through dGC13 clones (marked by the absence of yellow pigment) either in control flies or those expressing Atro75QN with the Rhodopsin1 driver and aged 28 days. Mask panels below each section exemplify clonal boundaries and PR no. for the ommatidia. Early signs of degeneration indicated by reduced complement of photoreceptors are detected specifically in the pigmented area (arrowhead). At this stage, inside d mutant clones all ommatidia are unaffected and display a wt arrangement (arrows). (B) Histograms showing the quantification of cell loss in eyes shown in (A). A statistically significant rescue is obtained both for the number of wt ommatidia (*P0.05 in two‐tailed t‐test) and for all other categories of ommatidia (χ2=44.76; P0.001 for 2 degrees of freedom)."
NCBI gene IDs:
"d: 33245
dachs: 33245
Atro: 46156
Rhodopsin1: 42367"
Figure legend: "(A) EM scan of a wt (left) and ftfd mutant ommatidium (right) of a ftfd clone after 14 days. Scale bar: 1 μm. High‐magnification panels (far right, top to bottom) display autophagosomes with undigested debris, damaged mitochondria and forming phagophores (arrowheads), found in ftfd mutant cells. Scale bar: 0.2 μm for zoom‐in panels."
NCBI gene IDs:
"ft: 33627"