In vitro differentiation of murine embryonic stem cells toward a renal lineage

Bruce, Stephen J.; Rea, Robert W; Steptoe, Anita L; Busslinger, Meinrad; Bertram, John F.; Perkins, Andrew

doi:10.1111/j.1432-0436.2006.00149.x

Cited by 108 publications

(63 citation statements)

References 68 publications

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“…45 The other prescribed a strict application of BMP4, BMP2, and BMP7 to ES cells grown in serum-free media. 46 In addition, yet another study showed renal proximal tubular progenitor cells can be differentiated from ES cells using activin-A and sorted for Brachyury (T). 47 These methods can be used to differentiate the cells before scaffold seeding, providing a more kidney-specific lineage, or integrated into the culture system, allowing the cells to form ECM-mediated structures as they grow and differentiate.…”

Section: Discussionmentioning

confidence: 99%

Embryonic Stem Cells Proliferate and Differentiate when Seeded into Kidney Scaffolds

Ross

Williams²,

Hamazaki³

et al. 2009

Journal of the American Society of Nephrology

366

266

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The scarcity of transplant allografts for diseased organs has prompted efforts at tissue regeneration using seeded scaffolds, an approach hampered by the enormity of cell types and complex architectures. Our goal was to decellularize intact organs in a manner that retained the matrix signal for differentiating pluripotent cells. We decellularized intact rat kidneys in a manner that preserved the intricate architecture and seeded them with pluripotent murine embryonic stem cells antegrade through the artery or retrograde through the ureter. Primitive precursor cells populated and proliferated within the glomerular, vascular, and tubular structures. Cells lost their embryonic appearance and expressed immunohistochemical markers for differentiation. Cells not in contact with the basement membrane matrix became apoptotic, thereby forming lumens. These observations suggest that the extracellular matrix can direct regeneration of the kidney, and studies using seeded scaffolds may help define differentiation pathways.

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Section: Discussionmentioning

confidence: 99%

Embryonic Stem Cells Proliferate and Differentiate when Seeded into Kidney Scaffolds

Ross

Williams²,

Hamazaki³

et al. 2009

Journal of the American Society of Nephrology

366

266

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“…Low passage number (P18) W9.5 ES cells were maintained in 15% fetal calf serum (FCS) on mitotically inactive mouse embryonic fibroblasts (MEFs) with 1000 U/mL LIF as described (Bruce et al 2007b). Differentiation was performed in Dulbecco's modified Eagle's medium (DMEM) containing 10% FCS in 1% methylcellulose (GIBCO 10912-012).…”

Section: Cell Culturing and Mouse Tissue Samplesmentioning

confidence: 99%

Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation

Dinger¹,

Amaral²,

Mercer³

et al. 2008

Genome Res.

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704

588

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The transcriptional networks that regulate embryonic stem (ES) cell pluripotency and lineage specification are the subject of considerable attention. To date such studies have focused almost exclusively on protein-coding transcripts. However, recent transcriptome analyses show that the mammalian genome contains thousands of long noncoding RNAs (ncRNAs), many of which appear to be expressed in a developmentally regulated manner. The functions of these remain untested. To identify ncRNAs involved in ES cell biology, we used a custom-designed microarray to examine the expression profiles of mouse ES cells differentiating as embryoid bodies (EBs) over a 16-d time course. We identified 945 ncRNAs expressed during EB differentiation, of which 174 were differentially expressed, many correlating with pluripotency or specific differentiation events. Candidate ncRNAs were identified for further characterization by an integrated examination of expression profiles, genomic context, chromatin state, and promoter analysis. Many ncRNAs showed coordinated expression with genomically associated developmental genes, such as Dlx1, Dlx4, Gata6, and Ecsit. We examined two novel developmentally regulated ncRNAs, Evx1as and Hoxb5/6as, which are derived from homeotic loci and share similar expression patterns and localization in mouse embryos with their associated protein-coding genes. Using chromatin immunoprecipitation, we provide evidence that both ncRNAs are associated with trimethylated H3K4 histones and histone methyltransferase MLL1, suggesting a role in epigenetic regulation of homeotic loci during ES cell differentiation. Taken together, our data indicate that long ncRNAs are likely to be important in processes directing pluripotency and alternative differentiation programs, in some cases through engagement of the epigenetic machinery.

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“…Furthermore, when injected into metanephric explants culture, primed EBs showed 100% incorporation into developing renal tubules. Similarly, murine ES cells primed in vitro with activin-A alone or BMP-4 differentiate into cells expressing markers of the intermediate mesoderm, early kidney development-as well as renal tubule-specific markers [60,61]. A recent study has shown that human amniotic-fluid derived stem cells are capable of forming early nephron structures (renal vesicles, S-and comma-shaped bodies) when injected into embryonic mouse kidneys.…”

Section: Embryonic Stem Cellsmentioning

confidence: 99%

Stem cell options for kidney disease

Hopkins

Rae

et al. 2008

The Journal of Pathology

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Chronic kidney disease (CKD) is increasing at the rate of 6-8% per annum in the US alone. At present, dialysis and transplantation remain the only treatment options. However, there is hope that stem cells and regenerative medicine may provide additional regenerative options for kidney disease. Such new treatments might involve induction of repair using endogenous or exogenous stem cells or the reprogramming of the organ to reinitiate development. This review addresses the current state of understanding with respect to the ability of non-renal stem cell sources to influence renal repair, the existence of endogenous renal stem cells and the biology of normal renal repair in response to damage. Understanding repair options via an understanding of renal developmentThe prevalence and incidence of chronic kidney disease (CKD) is increasing at 6-8% per annum in the USA alone, largely as a result of increased prevalence of diabetes and obesity [1]. To understand what might be possible with respect to cellular therapies or regenerative medicine for the kidney, one first needs to consider what is understood about normal renal development and response to injury. The kidney has been classically regarded as an organ with minimal cellular turnover and no capacity for regeneration. The subsequent identification of stem cells in a number of such organs, including the brain, has challenged this view. However, the dogma remains that the kidney reaches a maximal complement of nephrons and then loses these over time [2]. This dogma is drawn from our understanding of the development of this organ. The progenitor population during developmentThe kidney is mesodermal in origin and develops from two populations derived from intermediate mesoderm, the ureteric bud (UB) and the metanephric mesenchyme (MM). While an even broader potential had been proposed [3], genetic and lineage analyses have confirmed that the MM gives rise to all portions of the nephron other than the collecting ducts and also gives rise to elements of the renal interstitium [4][5][6]. The UB gives rise to the ureter and collecting ducts only. The MM is apparently not homogeneous but forms condensed mesenchyme around the tips of the branching UB. This cap mesenchyme (CM) contains self-renewing progenitors capable of generating all cells of the nephron other than the collecting ducts via an initial mesenchyme-epithelial transition (MET) event throughout the prenatal developmental period [6]. The continued expression of the transcription factor Six2 in CM is required for maintenance of this stem cell population during kidney development [5]. As the UB branches and extends through the MM, individual MET events occur at the underside of each tip to form a new nephron [2]. This nephron endowment therefore proceeds from the centre of the kidney out to the periphery, with the CM stem cell field remaining on the outer edge of the expanding organ. Endowment of new nephrons is restricted to prenatal development in humans, while in rodents it persists only until the imm...

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In vitro differentiation of murine embryonic stem cells toward a renal lineage

Cited by 108 publications

References 68 publications

Embryonic Stem Cells Proliferate and Differentiate when Seeded into Kidney Scaffolds

Embryonic Stem Cells Proliferate and Differentiate when Seeded into Kidney Scaffolds

Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation

Stem cell options for kidney disease

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