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Single cell data for"The cellular states and fates of shed intestinal cells" paper. Folder: Count_tables and Objects This folder contains BG subtracted UMI tables and metadata for both the fecal wash UMAP and the fecal/tissue enterocytes combined UMAP 1. BG_subtracted_count_table_all_Fecal_cells_before_filt.txt - BG subtracted UMI table of all cells before Seurat filtration and analysis 2. BG_subtracted_count_table_all_Fecal_cells_after_filt.txt - BG subtracted UMI table of all cells after Seurat filtration and analysis. 3. Metadata_all_Fecal_cells_after_filteration.txt - Metadata for "BG_subtracted_count_table_all_Fecal_cells_after_filt.txt" 4. Combine_all_Fecal_cells_Obj.rds - Seurat Object for BG_subtracted_count_table_all_Fecal_cells_after_filt.txt 5. BG_subtracted_count_table_all_Enterocytes_before_filt.txt - BG subtracted UMI table of all cells before Seurat filtration and analysis 6. BG_subtracted_count_table_all_Enterocytes_after_filt.txt - BG subtracted UMI table of all cells after Seurat filtration and analysis. 7. Metadata_all_Enterocytes_after_filteration.txt - Metadata for "BG_subtracted_count_table_all_Enterocytes_after_filt.txt" 8. Combine_Enterocytes_Obj.rds - Seurat Object for BG_subtracted_count_table_all_Enterocytes_after_filt.txt

SummaryWe recently showed that intravenous infusion of mouse or human, fetal or adult lung cells following conditioning of recipient mice leads to lung chimerism within alveolar and bronchiolar lineages, in distinct ‘patches’ containing both epithelial and endothelial cells. We show here, using R26R-Confetti mice as donors, that these multi-lineage patches are derived from a single lung progenitor. FACS of adult mouse lung cells revealed that the putative patch-forming progenitors co-express the endothelial marker CD31 (PECAM-1) and the epithelial marker CD326 (EPCAM). Transplantation of lung cells from transgenic Cre/lox mice expressing membrane GFP under the VEcad promoter (VEcad-Cre-mTmG), led to GFP+ patches comprising both GFP+ endothelial and epithelial cells in vivo, and in ex-vivo culture of CD326+CD31+ progenitors. Single cell mRNAseq of CD326+CD31+ lung cells revealed a subpopulation expressing canonical epithelial and endothelial genes. Such double positive GFP+NKX2.1+SOX17+ cells were also deteceted by immuno-histologial staining in lungs of VEcad-Cre-nTnG (expressing nulear GFP) mice in proximity to blood vessels. These findings provide new insights on lung progenitros and lung development and suggest a potential novel approach for lung regeneration.

BackgroundThe significant risks posed to mothers and fetuses by COVID-19 in pregnancy have sparked a worldwide debate surrounding the pros and cons of antenatal SARS-CoV-2 inoculation, as we lack sufficient evidence regarding vaccine effectiveness in pregnant women and their offspring. We aimed to provide substantial evidence for the effect of BNT162b2 mRNA vaccine versus native infection on maternal humoral, as well as transplacentally acquired fetal immune response, potentially providing newborn protection.MethodsA multicenter study where parturients presenting for delivery were recruited at 8 medical centers across Israel and assigned to three study groups: vaccinated (n=86); PCR confirmed SARS-CoV-2 infected during pregnancy (n=65), and unvaccinated non-infected controls (n=62). Maternal and fetal blood samples were collected from parturients prior to delivery and from the umbilical cord following delivery, respectively. Sera IgG and IgM titers were measured using Milliplex MAP SARS-CoV-2 Antigen Panel (for S1, S2, RBD and N).ResultsBNT162b2 mRNA vaccine elicits strong maternal humoral IgG response (Anti-S and RBD) that crosses the placenta barrier and approaches maternal titers in the fetus within 15 days following the first dose. Maternal to neonatal anti-COVID-19 antibodies ratio did not differ when comparing sensitization (vaccine vs. infection). IgG transfer rate was significantly lower for third-trimester as compared to second trimester infection. Lastly, fetal IgM response was detected in 5 neonates, all in the infected group.ConclusionsAntenatal BNT162b2 mRNA vaccination induces a robust maternal humoral response that effectively transfers to the fetus, supporting the role of vaccination during pregnancy.

The peptidyl-prolyl cis-trans isomerase, Pin1, acts as a unified signaling hub that is exploited in cancer to activate oncogenes and inactivate tumor suppressors, in particular through up-regulation of c-Myc target genes. However, despite considerable efforts, Pin1 has remained an elusive drug target. Here, we screened an electrophilic fragment library to discover covalent inhibitors targeting Pin1’s active site nucleophile - Cys113, leading to the development of Sulfopin, a double-digit nanomolar Pin1 inhibitor. Sulfopin is highly selective for Pin1, as validated by two independent chemoproteomics methods, achieves potent cellular andin vivotarget engagement, and phenocopies genetic knockout of Pin1. Although Pin1 inhibition had a modest effect on viability in cancer cell cultures, Sulfopin induced downregulation of c-Myc target genes and reduced tumor initiation and tumor progression in murine and zebrafish models of MYCN-driven neuroblastoma. Our results suggest that Sulfopin is a suitable chemical probe for assessing Pin1-dependent pharmacology in cells andin vivo. Moreover, these studies indicate that Pin1 should be further investigated as a potential cancer target.