Transcription factor TFCP2L1 patterns cells in the mouse kidney collecting ducts

Werth, Max; Schmidt‐Ott, Kai M.; Leete, Thomas; Qiu, Andong; Hinze, Christian; Viltard, Mélanie; Paragas, Neal; Shawber, Carrie J.; Yu, Wenqiang; Lee, Peter; Chen, Xia; Sarkar, Abby; Mu, Weiyi; Rittenberg, Alexander; Lin, Chyuan Sheng; Kitajewski, Jan; Al‐Awqati, Qais; Barasch, Jonathan

doi:10.7554/elife.24265

Cited by 64 publications

(65 citation statements)

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“…This suggests that cluster 8 is likely to be a transitional cell population and not a proliferating progenitor cell. Thus, in vivo lineage tagging analysis confirmed transitions of PC and IC cells not only during development (15–17) but also in the adult collecting duct via a newly identified transitional cell type.…”

Section: Fluorescent Lineage Tracing Confirms Collecting Duct Cell Plmentioning

confidence: 60%

“…4C). This experimental model allowed us to study only the IC to PC transition occurring in adult mice as opposed to those occurring during embryogenesis (15). We found that NOTCH expression disrupted cellular patterning.…”

Section: Collecting Duct Cell Plasticity Driven By Notch Ligand Andmentioning

confidence: 99%

“…Most cell plasticity in the adult has been observed in the context of terminal differentiation of progenitor cells, best described in the blood and intestine (14). Yet, such cellular transitions also may be ongoing in collecting duct development (15–17) or even in the adult collecting duct. For example, subtypes of intercalated cells (ICs) can change their functional polarity, and even stem cell-like populations originating from the principal cell types (PCs) may persist in the adult collecting duct and respond to the external stimuli (18, 19), but definitive isolation and definition of these plastic cells is lacking.…”

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confidence: 99%

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Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease

Park

Shrestha

Qiu

et al. 2018

Science

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Our understanding of kidney disease pathogenesis is limited by an incomplete molecular characterization of the cell types responsible for the organ’s multiple homeostatic functions. To help fill this knowledge gap, we characterized 57,979 cells from healthy mouse kidneys using unbiased single-cell RNA sequencing. Based on gene expression patterns, we infer that inherited kidney diseases that arise from distinct genetic mutations but have similar phenotypic manifestations share the same cell of origin. We also found that the kidney collecting duct in adult mice generates a spectrum of cell types via a newly identified transitional cell. Computational cell trajectory analysis and in vivo lineage tracing revealed that intercalated cells and principal cells undergo transitions mediated by the Notch signaling pathway. In mouse and human kidney disease, these transitions were shifted toward a principal cell fate and were associated with metabolic acidosis.

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Section: Fluorescent Lineage Tracing Confirms Collecting Duct Cell Plmentioning

confidence: 60%

Section: Collecting Duct Cell Plasticity Driven By Notch Ligand Andmentioning

confidence: 99%

mentioning

confidence: 99%

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Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease

Park

Shrestha

Qiu

et al. 2018

Science

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922

936

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“…In kidney, cell type transition has been only studied in development and between subtypes of intercalated cells (11)(12)(13)(14).…”

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confidence: 99%

Comprehensive single cell RNAseq analysis of the kidney reveals novel cell types and unexpected cell plasticity

Park

Shrestha

Qiu

et al. 2017

Preprint

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Abstract:A key limitations to understand kidney function and disease development has been that specific cell types responsible for specific homeostatic kidney function or disease phenotypes have not been defined at the molecular level.To fill this gap, we characterized 57,979 cells from healthy mouse kidneys using unbiased single-cell RNA sequencing. We show that genetic mutations that present with similar phenotypes mostly affect genes that are expressed in a single unique differentiated cell type. On the other hand, we found unexpected cell plasticity of epithelial cells in the final segment of the kidney (collecting duct) that is responsible for final composition of the urine. Using All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

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“…The result of axial crease compaction and hence global volumetric compaction of ECM is a considerable increase in cell density from the as-patterned state -MDCK cells were initially distributed along prospective creases at an average spacing of ~30 µm, and condensed down to a spacing of 9.0 µm ± 12% CV (n = 10) after 40 hr. This spacing is approximately equivalent to the ~8 µm cell spacing seen in E18 mouse collecting ducts (28), and far closer than the ~17 µm spacing that would be expected purely due to cell proliferation over this time. In addition to axial crease compaction, the tight, ordered spacing of cells could be reinforced by axial cell migration along creases, and/or axially-biased cell intercalation (29) -mechanisms that we are currently examining.…”

Section: Resultsmentioning

confidence: 49%

Kinomorphs: Shape-shifting tissues for developmental engineering

Viola

Porter

Gupta

et al. 2019

Preprint

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Current methods for building tissues usually start with a non-biological blueprint, or rely on self-organization, which does not extend to organ-scales. This has limited the construction of large tissues that simultaneously encode fine-scale cell organization. Here we bridge scales by mimicking developmental dynamics using “kinomorphs”, tissue scaffolds that undergo globally programmed shape and density changes to trigger local self-organization of cells in many locations at once. In this first report, we focus on mimicking the extracellular matrix (ECM) compaction and division into leaflets that occurs in kidney collecting duct development. We start by creating single-cell resolution cell patterns in ECM-mimetic hydrogels that are >10x larger than previously described, by leveraging photo-lithographic technology. These patterns are designed to mimic the branch geometry of the embryonic kidney collecting duct tree. We then predict the shape dynamics of kinomorphs driven by cell contractility-based compaction of the ECM using kinematic origami simulations. We show that these dynamics spur centimeter-scale assembly of structurally mature ~50 μm-diameter epithelial tubules that are locally self-organized, but globally programmed. Our approach prescribes tubule network geometry at ~5x smaller length-scales than currently possible using 3D printing, and at local cell densities comparable to in vivo tissues. Kinomorphs could be used to scaffold and “plumb” arrays of organoids in the future, by guiding the morphogenesis of epithelial networks. Such hybrid globally programmed/locally self-organized tissues address a major gap in our ability to recapitulate organ-scale tissue structure.Significance StatementEngineers are attempting to build tissues that mimic human diseases outside of the body. Although stem cells can be coaxed to form small organoids with a diversity of cell types, they do not properly organize over large distances by themselves. We report a strategy to mimic developmental processes using dynamic materials that attempt to guide a cellular “blueprint” towards a more complex tissue endpoint. We call these materials kinomorphs, combining the Greek kinó (propel, drive) and morfí (form, shape), since they seek to shepherd both the shape and developmental trajectory of cell collectives within them. Kinomorphs could pave the way towards organ-scale synthetic tissues built through a hybrid of engineering and self-organization strategies.

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Transcription factor TFCP2L1 patterns cells in the mouse kidney collecting ducts

Cited by 64 publications

References 68 publications

Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease

Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease

Comprehensive single cell RNAseq analysis of the kidney reveals novel cell types and unexpected cell plasticity

Kinomorphs: Shape-shifting tissues for developmental engineering

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