Progressive Recruitment of Mesenchymal Progenitors Reveals a Time-Dependent Process of Cell Fate Acquisition in Mouse and Human Nephrogenesis

Lindström, Nils O.; Brandine, Guilherme de Sena; Tran, Thi Thu Huong; Ransick, Andrew; Suh, Gio C.; Guo, Jinjin; Kim, Albert D.; Parvez, Riana K.; Ruffins, Seth; Rutledge, Elisabeth A.; Thornton, Matthew E.; Grubbs, Brendan H.; McMahon, Jill A.; Smith, Andrew D.; McMahon, Andrew P.

doi:10.1016/j.devcel.2018.05.010

Cited by 180 publications

(233 citation statements)

References 43 publications

Supporting

Mentioning

208

Contrasting

Order By: Relevance

“…Dissociation of the adult mouse kidney into a representative set of single cells presented a significant challenge beyond protocols extracting cortical nephron progenitor cells from the surface of fetal and newborn mouse kidney (Lindström et al, 2018a). To avoid stress artefacts, we followed a 'cold dissociation' strategy, built around Bacillus licheniformis cold active protease (CAP), which had been successfully used to dissociate newborn (p1) mouse kidneys (Adam et al, 2017), monitoring cell yields by fluorescence-activated cell sorting (see below) and a quantitative PCR assessment of cDNA for cell-type specific markers comparing to undissociated tissue.…”

Section: Adult Mouse Kidney Cell Dissociationmentioning

confidence: 99%

Single Cell Profiling Reveals Sex, Lineage and Regional Diversity in the Mouse Kidney

Ransick

Lindström

Liu

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

Chronic kidney disease affects 10% of the population with notable differences in ethnic and sex-related susceptibility to kidney injury and disease. Kidney dysfunction leads to significant morbidity and mortality, and chronic disease in other organ systems. A mouse organ-centered understanding underlies rapid progress in human disease modeling, and cellular approaches to repair damaged systems. To enhance an understanding of the mammalian kidney, we combined anatomy-guided single cell RNA sequencing of the adult male and female mouse kidney with in situ expression studies and cell lineage tracing. These studies reveal cell diversity and marked sex differences, distinct organization and cell composition of nephrons dependent on the time of nephron specification, and lineage convergence, in which contiguous functionally-related cell types are specified from nephron and collecting system progenitor populations. A searchable database integrating findings to highlight gene-cell relationships in a normal anatomical framework will facilitate study of the mammalian kidney.

show abstract

Section: Adult Mouse Kidney Cell Dissociationmentioning

confidence: 99%

Single Cell Profiling Reveals Sex, Lineage and Regional Diversity in the Mouse Kidney

Ransick

Lindström

Liu

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…We related the cell clusters from D29 human kidney organoids (ThF line) to human tissue by comparing them to fetal kidney from the first (8 weeks) and second (17 weeks) trimesters (Lindström et al, 2018b;, and to adult kidney (Fig. 1C, right).…”

Section: Mature Organoids Most Closely Resemble Fetal Kidneymentioning

confidence: 99%

Kidney organoid reproducibility across multiple human iPSC lines and diminished off target cells after transplantation revealed by single cell transcriptomics

Subramanian

Sidhom

Emani

et al. 2019

Preprint

View full text Add to dashboard Cite

Human iPSC-derived kidney organoids have the potential to revolutionize discovery, but assessing their consistency and reproducibility across iPSC lines, and reducing the generation of off-target cells remain an open challenge. Here, we used single cell RNA-Seq (scRNA-Seq) to profile 415,775 cells to show that organoid composition and development are comparable to human fetal and adult kidneys. Although cell classes were largely reproducible across iPSC lines, time points, protocols, and replicates, cell proportions were variable between different iPSC lines. Off-target cell proportions were the most variable. Prolonged in vitro culture did not alter cell types, but organoid transplantation under the mouse kidney capsule diminished offtarget cells. Our work shows how scRNA-seq can help score organoids for reproducibility, faithfulness and quality, that kidney organoids derived from different iPSC lines are comparable surrogates for human kidney, and that transplantation enhances their formation by diminishing off-target cells.

show abstract

“…These studies confirmed increased expression of Cyp26b1 in ECs compared to non-ECs (Supplemental Fig. 1) (Du et al, 2015;Du et al, 2017;Guo et al, 2019;Hochane et al, 2019;Lindstrom et al, 2018;Sabbagh et al, 2018;Tabula Muris et al, 2018).…”

Section: Cyp26b1 Is Highly Enriched In Lung and Kidney Ecsmentioning

confidence: 53%

Cyp26b1 is required for proper airway epithelial differentiation during lung development

Daniel

Sutton

Htike

et al. 2019

Preprint

View full text Add to dashboard Cite

Proper organ development depends on coordinated communication between multiple cell types. Retinoic acid (RA) is an autocrine and paracrine signaling molecule critical for the development of most organs including the lung. Both RA excess and deficiency lead to drastic alterations in embryogenesis, often culminating in embryonic or neonatal lethality. Therefore, RA levels must be spatially and temporally titrated to ensure proper organogenesis. Despite extensive work detailing the effects of RA deficiency in early lung morphogenesis, little is known about how RA levels are modulated during late lung development. Here, we investigate the role of the RA catabolizing protein Cyp26b1 in lung development. Cyp26b1 is highly enriched in lung endothelial cells (ECs) throughout the course of development. We find that loss of Cyp26b1 impacts differentiation of the distal epithelium without appreciably affecting proximal airways, EC lineages, or stromal populations. Cyp26b1−/− lungs exhibit an increase in cellular density, with an expansion of distal progenitors at the expense of alveolar type 1 (AT1) cells, which culminates in neonatal death. Exogenous administration of RA in late gestation was able to partially reproduce this defect in epithelial differentiation; however, transcriptional analyses of Cyp26b1−/− lungs and RA-treated lungs reveal separate, but overlapping, transcriptional responses. These data suggest that the defects observed in Cyp26b1−/− lungs are caused by both RA-dependent and RA-independent mechanisms. This work highlights critical cellular crosstalk during lung development involving a crucial role for Cyp26b1-expressing endothelium, and identifies a novel RA rheostat in lung development.HIGHLIGHTSCyp26b1 is highly expressed in lung ECs throughout developmentCyp26b1-null lungs fail to undergo proper differentiation of distal epithelium leading to an increase in progenitors and AT2 cells at the expense of AT1 cellsFunctional and transcriptional analyses suggest both RA-dependent and RA-independent mechanisms

show abstract

Progressive Recruitment of Mesenchymal Progenitors Reveals a Time-Dependent Process of Cell Fate Acquisition in Mouse and Human Nephrogenesis

Cited by 180 publications

References 43 publications

Single Cell Profiling Reveals Sex, Lineage and Regional Diversity in the Mouse Kidney

Single Cell Profiling Reveals Sex, Lineage and Regional Diversity in the Mouse Kidney

Kidney organoid reproducibility across multiple human iPSC lines and diminished off target cells after transplantation revealed by single cell transcriptomics

Cyp26b1 is required for proper airway epithelial differentiation during lung development

Contact Info

Product

Resources

About