scholarly journals Chromatin accessibility and microRNA expression in nephron progenitor cells during kidney development

Genomics ◽  
2021 ◽  
Author(s):  
Andrew Clugston ◽  
Andrew Bodnar ◽  
Débora Malta Cerqueira ◽  
Yu Leng Phua ◽  
Alyssa Lawler ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Kidney Development ◽  
Chromatin Accessibility ◽  
Microrna Expression ◽  
Nephron Progenitor

scholarly journals Chromatin accessibility and microRNA expression in nephron progenitor cells during kidney development

2021 ◽  
Author(s):  
Andrew Clugston ◽  
Andrew Bodnar ◽  
Débora Malta Cerqueira ◽  
Yu Leng Phua ◽  
Alyssa Lawler ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Kidney Development ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Microrna Expression ◽  
Genome Wide ◽  
Extracellular Matrix Interactions ◽  
Genomic Regions ◽  
Nephron Progenitor ◽  
Accessible Chromatin

AbstractMammalian nephrons originate from a population of nephron progenitor cells (NPCs), and it is known that NPCs’ transcriptomes change throughout nephrogenesis during healthy kidney development. To characterize chromatin accessibility and microRNA (miRNA) expression throughout this process, we collected NPCs from mouse kidneys at embryonic day 14.5 (E14.5) and postnatal day zero (P0) and assayed cells for transposase-accessible chromatin and small RNA expression. We observe 46,374 genomic regions of accessible chromatin, with 2,103 showing significant changes in accessibility between E14.5 and P0. In addition, we detect 1,104 known microRNAs, with 114 showing significant changes in expression. Genome-wide, changes in DNA accessibility and microRNA expression highlight biological processes like cellular differentiation, cell migration, extracellular matrix interactions, and developmental signaling pathways such as Notch. Furthermore, our data identify novel candidate cis-regulatory elements for Eya1 and Pax8, both genes with a role in NPC differentiation; we also associate expression-changing microRNAs, including let-7-5p, miR-125b-5p, miR-181a-2-3p, and miR-9-3p, with candidate cis-regulatory elements. Overall, our data characterize NPCs during kidney development and point out new candidate regulatory elements for genes and microRNA with key roles in nephrogenesis.

scholarly journals Premature differentiation of nephron progenitor cell and dysregulation of gene pathways critical to kidney development in a model of preterm birth

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aleksandra Cwiek ◽  
Masako Suzuki ◽  
Kimberly deRonde ◽  
Mark Conaway ◽  
Kevin M. Bennett ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Progenitor Cells ◽  
Kidney Development ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Neonatal Morbidity ◽  
Expression Of Genes ◽  
Nephron Progenitor ◽  
Lower Expression ◽  
Nephrogenic Zone

AbstractPreterm birth is a leading cause of neonatal morbidity. Survivors have a greater risk for kidney dysfunction and hypertension. Little is known about the molecular changes that occur in the kidney of individuals born preterm. Here, we demonstrate that mice delivered two days prior to full term gestation undergo premature cessation of nephrogenesis, resulting in a lower glomerular density. Kidneys from preterm and term groups exhibited differences in gene expression profiles at 20- and 27-days post-conception, including significant differences in the expression of fat-soluble vitamin-related genes. Kidneys of the preterm mice exhibited decreased proportions of endothelial cells and a lower expression of genes promoting angiogenesis compared to the term group. Kidneys from the preterm mice also had altered nephron progenitor subpopulations, early Six2 depletion, and altered Jag1 expression in the nephrogenic zone, consistent with premature differentiation of nephron progenitor cells. In conclusion, preterm birth alone was sufficient to shorten the duration of nephrogenesis and cause premature differentiation of nephron progenitor cells. These candidate genes and pathways may provide targets to improve kidney health in preterm infants.

scholarly journals Genomic characterization of Wilms' tumor suppressor 1 targets in nephron progenitor cells during kidney development

Development ◽  
2010 ◽  
Vol 137 (7) ◽  
pp. 1189-1203 ◽  
Author(s):  
S. Hartwig ◽  
J. Ho ◽  
P. Pandey ◽  
K. MacIsaac ◽  
M. Taglienti ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Progenitor Cells ◽  
Kidney Development ◽  
Wilms Tumor ◽  
Genomic Characterization ◽  
Nephron Progenitor

scholarly journals Three Optimized Methods for In Situ Quantification of Progenitor Cell Proliferation in Embryonic Kidneys Using BrdU, EdU, and PCNA

2019 ◽  
Vol 6 ◽  
pp. 205435811987193
Author(s):  
Rosalie E. O’Hara ◽  
Michel G. Arsenault ◽  
Blanca P. Esparza Gonzalez ◽  
Ashley Patriquen ◽  
Sunny Hartwig
Keyword(s):  
Cell Proliferation ◽  
Progenitor Cells ◽  
Kidney Development ◽  
Fluorescence Labeling ◽  
Nuclear Antigen ◽  
Ureteric Bud ◽  
Proliferating Cells ◽  
Advantages And Disadvantages ◽  
Nephron Progenitor

Background: Nephron progenitor cells derived from the metanephric mesenchyme undergo a complex balance of self-renewal and differentiation throughout kidney development to give rise to the mature nephron. Cell proliferation is an important index of progenitor population dynamics. However, accurate and reproducible in situ quantification of cell proliferation within progenitor populations can be technically difficult to achieve due to the complexity and harsh tissue treatment required of certain protocols. Objective: To optimize and compare the performance of the 3 most accurate S phase–specific labeling methods used for in situ detection and quantification of nephron progenitor and ureteric bud cell proliferation in the developing kidney, namely, 5-bromo-2’-deoxyuridine (BrdU), 5-ethynyl-2’-deoxyuridine (EdU), and proliferating cell nuclear antigen (PCNA). Methods: Protocols for BrdU, EdU, and PCNA were optimized for fluorescence labeling on paraformaldehyde-fixed, paraffin-embedded mouse kidney tissue sections, with co-labeling of nephron progenitor cells and ureteric bud with Six2 and E-cadherin antibodies, respectively. Image processing and analysis, including quantification of proliferating cells, were carried out using free ImageJ software. Results: All 3 methods detect similar ratios of nephron progenitor and ureteric bud proliferating cells. The BrdU staining protocol is the lengthiest and most complex protocol to perform, requires tissue denaturation, and is most subject to interexperimental signal variability. In contrast, bound PCNA and EdU protocols are relatively more straightforward, consistently yield clear results, and far more easily lend themselves to co-staining; however, the bound PCNA protocol requires substantive additional postexperimental analysis to distinguish the punctate nuclear PCNA staining pattern characteristic of proliferating cells. Conclusions: All 3 markers exhibit distinct advantages and disadvantages in quantifying cell proliferation in kidney progenitor populations, with EdU and PCNA protocols being favored due to greater technical ease and reproducibility of results associated with these methods.

scholarly journals Asynchronous mixing of kidney progenitor cells potentiates nephrogenesis in organoids

2019 ◽  
Author(s):  
Ashwani K. Gupta ◽  
Prasenjit Sarkar ◽  
Xinchao Pan ◽  
Thomas Carroll ◽  
Leif Oxburgh
Keyword(s):  
Progenitor Cells ◽  
Kidney Development ◽  
Graft Function ◽  
Kidney Tissue ◽  
Systemic Circulation ◽  
Short Wave ◽  
Directed Differentiation ◽  
Kidney Capsule ◽  
Long Term Study ◽  
Nephron Progenitor

ABSTRACTRecent years have seen rapid advances in directed differentiation of human pluripotent stem cells (PSCs) to kidney cells. However, a fundamental difficulty in emulating kidney tissue formation is that kidney development is iterative. Recent studies argue that the human nephron forms through gradual contribution of nephron progenitor cells whose differentiation fates depend on the time at which they are recruited. We show that the majority of PSC-derived nephron progenitor cells differentiated in a short wave in organoid formation and to improve fidelity of PSC-derived organoids, we emulated the asynchronous mix found in the fetal kidney by combining cells differentiated at different times in the same organoid. Asynchronous mixing promoted nephrogenesis, and lineage marking data showed that proximal and distal nephron components preferentially derive from cell populations differentiated at distinct times. When engrafted under the kidney capsule these heterochronic organoids were vascularized and displayed essential features of kidney tissue. Micro-CT and injection of a circulating vascular marker demonstrated that engrafted kidney tissue was connected to the systemic circulation by 2 weeks after engraftment. Proximal tubule glucose uptake was confirmed using intravenous injection of fluorescent dextran. Despite these promising measures of graft function, overgrowth of stromal cells prevented long-term study, and we propose that this is a technical feature of the engraftment procedure rather than a specific shortcoming of the directed differentiation because kidney organoids derived from primary cells and whole embryonic kidneys develop the same stromal overgrowth when engrafted under the kidney capsule.

scholarly journals Repression of Interstitial Identity in Nephron Progenitor Cells by Pax2 Establishes the Nephron-Interstitium Boundary during Kidney Development

2017 ◽  
Vol 41 (4) ◽  
pp. 349-365.e3 ◽  
Author(s):  
Natalie Naiman ◽  
Kaoru Fujioka ◽  
Mari Fujino ◽  
M. Todd Valerius ◽  
S. Steven Potter ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Kidney Development ◽  
Nephron Progenitor

scholarly journals Premature differentiation of nephron progenitors and dysregulation of gene pathways critical to kidney development in a model of preterm birth

2021 ◽  
Author(s):  
Aleksandra Cwiek ◽  
Masako Suzuki ◽  
Kimberly deRonde ◽  
Mark Conaway ◽  
Kevin Bennett ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Progenitor Cells ◽  
Kidney Development ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Neonatal Morbidity ◽  
Expression Of Genes ◽  
Nephron Progenitors ◽  
Nephron Progenitor ◽  
Lower Expression

Abstract Preterm birth is a leading cause of neonatal morbidity. Survivors have a greater risk for kidney dysfunction and hypertension. Little is known about the molecular changes that occur in the kidney of individuals born preterm. Here, we demonstrate that mice delivered two days prior to full term gestation undergo premature cessation of nephrogenesis, resulting in a lower glomerular density. Kidneys from preterm and term groups exhibited differences in gene expression profiles at 20- and 27-days post-conception, including significant differences in expression of fat-soluble vitamin-related genes. Kidneys of the preterm mice exhibited decreased proportions of endothelial cells and a lower expression of genes promoting angiogenesis compared to the term group. Kidneys from the preterm mice also had altered nephron progenitor subpopulations, early Six2 depletion, and altered Jag1 expression in the nephrogenic zone, consistent with premature differentiation of nephron progenitor cells. In conclusion, preterm birth alone was sufficient to shorten the duration of nephrogenesis and cause premature differentiation of nephron progenitor cells. These candidate genes and pathways may provide targets to improve kidney health in preterm infants.

scholarly journals Troy/TNFRSF19 marks epithelial progenitor cells during mouse kidney development that continue to contribute to turnover in adult kidney

2017 ◽  
Vol 114 (52) ◽  
pp. E11190-E11198 ◽  
Author(s):  
Frans Schutgens ◽  
Maarten B. Rookmaaker ◽  
Francis Blokzijl ◽  
Ruben van Boxtel ◽  
Robert Vries ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Progenitor Cell ◽  
Kidney Development ◽  
Collecting Duct ◽  
Adult Kidney ◽  
Cell Property ◽  
Developing Kidney ◽  
Nephron Progenitor ◽  
Epithelial Progenitor Cells

During kidney development, progressively committed progenitor cells give rise to the distinct segments of the nephron, the functional unit of the kidney. Similar segment-committed progenitor cells are thought to be involved in the homeostasis of adult kidney. However, markers for most segment-committed progenitor cells remain to be identified. Here, we evaluate Troy/TNFRSF19 as a segment-committed nephron progenitor cell marker. Troy is expressed in the ureteric bud during embryonic development. During postnatal nephrogenesis, Troy+ cells are present in the cortex and papilla and display an immature tubular phenotype. Tracing of Troy+ cells during nephrogenesis demonstrates that Troy+ cells clonally give rise to tubular structures that persist for up to 2 y after induction. Troy+ cells have a 40-fold higher capacity than Troy− cells to form organoids, which is considered a stem cell property in vitro. In the adult kidney, Troy+ cells are present in the papilla and these cells continue to contribute to collecting duct formation during homeostasis. The number of Troy-derived cells increases after folic acid-induced injury. Our data show that Troy marks a renal stem/progenitor cell population in the developing kidney that in adult kidney contributes to homeostasis, predominantly of the collecting duct, and regeneration.

scholarly journals Directed Differentiation of Pluripotent Stem Cells into Kidney

2015 ◽  
Vol 10s1 ◽  
pp. BMI.S20055 ◽  
Author(s):  
Ryuji Morizane ◽  
Albert Q. Lam
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Kidney Development ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Directed Differentiation ◽  
Metanephric Mesenchyme ◽  
Nephron Progenitor

Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), represent an ideal substrate for regenerating kidney cells and tissue lost through injury and disease. Recent studies have demonstrated the ability to differentiate PSCs into populations of nephron progenitor cells that can organize into kidney epithelial structures in three-dimensional contexts. While these findings are highly encouraging, further studies need to be performed to improve the efficiency and specificity of kidney differentiation. The identification of specific markers of the differentiation process is critical to the development of protocols that effectively recapitulate nephrogenesis in vitro. In this review, we summarize the current studies describing the differentiation of ESCs and iPSCs into cells of the kidney lineage. We also present an analysis of the markers relevant to the stages of kidney development and differentiation and propose a new roadmap for the directed differentiation of PSCs into nephron progenitor cells of the metanephric mesenchyme.

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