Combination of small molecules enhances differentiation of mouse embryonic stem cells into intermediate mesoderm through BMP7-positive cells

Mae, Shin-Ichi; Shirasawa, Sakiko; Yoshie, Susumu; Sato, Fumi; Kanoh, Yoshiya; Ichikawa, Hinako; Yokoyama, Tetsuji; Yue, Fengming; Tomotsune, Daihachiro; Sasaki, Katsunori

doi:10.1016/j.bbrc.2010.02.111

Cited by 47 publications

(30 citation statements)

References 35 publications

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“…Regardless of the duration of CHIR pretreatment, the proportion of cells expressing PAX2 significantly decreased after day 4 of differentiation, with ,10% of cells at day 7 retaining PAX2 expression. Because previous studies have identified a role for BMP7 in inducing IM cells, 5,14,16,17 we next determined whether the addition of BMP7 to FGF2 and RA could enhance IM cell differentiation. In contrast to these other reports, we found that the addition of BMP7 significantly To determine the reproducibility of our protocol in different hPSC lines, we tested the combination of CHIR induction for 36 hours followed by the addition of FGF2 and RA in three hESC lines and two hiPSC lines.…”

Section: Fgf2 Induces Pax2 Expression In Chir-induced Cellsmentioning

confidence: 99%

“…Although several studies have attempted to differentiate mouse ESCs into kidney cells, [4][5][6][7][8][9][10][11][12][13][14][15] only a few studies have reported protocols in hESCs and hiPSCs. [16][17][18][19] These previous reports have produced cells that share characteristics expected of human kidney progenitor or epithelial cells, although the identities of these differentiated cells have yet to be conclusively verified.…”

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confidence: 99%

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Rapid and Efficient Differentiation of Human Pluripotent Stem Cells into Intermediate Mesoderm That Forms Tubules Expressing Kidney Proximal Tubular Markers

Lam

Freedman

Morizane

et al. 2014

Journal of the American Society of Nephrology

275

228

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Human pluripotent stem cells (hPSCs) can generate a diversity of cell types, but few methods have been developed to derive cells of the kidney lineage. Here, we report a highly efficient system for differentiating human embryonic stem cells and induced pluripotent stem cells (referred to collectively as hPSCs) into cells expressing markers of the intermediate mesoderm (IM) that subsequently form tubule-like structures. Treatment of hPSCs with the glycogen synthase kinase-3b inhibitor CHIR99021 induced BRACHYURY + MIXL1 + mesendoderm differentiation with nearly 100% efficiency. In the absence of additional exogenous factors, CHIR99021-induced mesendodermal cells preferentially differentiated into cells expressing markers of lateral plate mesoderm with minimal IM differentiation. However, the sequential treatment of hPSCs with CHIR99021 followed by fibroblast growth factor-2 and retinoic acid generated PAX2 + LHX1 + cells with 70%-80% efficiency after 3 days of differentiation. Upon growth factor withdrawal, these PAX2 + LHX1 + cells gave rise to apically ciliated tubular structures that coexpressed the proximal tubule markers Lotus tetragonolobus lectin, N-cadherin, and kidney-specific protein and partially integrated into embryonic kidney explant cultures. With the addition of FGF9 and activin, PAX2 + LHX1 + cells specifically differentiated into cells expressing SIX2, SALL1, and WT1, markers of cap mesenchyme nephron progenitor cells. Our findings demonstrate the effective role of fibroblast growth factor signaling in inducing IM differentiation in hPSCs and establish the most rapid and efficient system whereby hPSCs can be differentiated into cells with features characteristic of kidney lineage cells.

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Section: Fgf2 Induces Pax2 Expression In Chir-induced Cellsmentioning

confidence: 99%

mentioning

confidence: 99%

Rapid and Efficient Differentiation of Human Pluripotent Stem Cells into Intermediate Mesoderm That Forms Tubules Expressing Kidney Proximal Tubular Markers

Lam

Freedman

Morizane

et al. 2014

Journal of the American Society of Nephrology

275

228

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“…Protocols for directed differentiation of hPSCs have now been developed for many cell types. In the kidney field, early attempts at generating specific kidney tissues began using mouse ESCs (Yamamoto et al, 2006;Steenhard et al, Vigneau et al, 2007;Morizane et al, 2009;Mae et al, 2010;Ren et al, 2010;Nishikawa et al, 2012; reviewed by Takasato et al, 2014b). Early attempts at directed differentiation of hPSCs into kidney tissues, focused on identification of specific endpoints, including podocytes (Song et al, 2012) and proximal tubules (Narayanan et al, 2013).…”

Section: Implications For Recreating the Kidney In Vitromentioning

confidence: 99%

The origin of the mammalian kidney: implications for recreating the kidney in vitro

2015

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The mammalian kidney, the metanephros, is a mesodermal organ classically regarded as arising from the intermediate mesoderm (IM). Indeed, both the ureteric bud (UB), which gives rise to the ureter and the collecting ducts, and the metanephric mesenchyme (MM), which forms the rest of the kidney, derive from the IM. Based on an understanding of the signalling molecules crucial for IM patterning and kidney morphogenesis, several studies have now generated UB or MM, or both, in vitro via the directed differentiation of human pluripotent stem cells. Although these results support the IM origin of the UB and the MM, they challenge the simplistic view of a common progenitor for these two populations, prompting a reanalysis of early patterning events within the IM. Here, we review our understanding of the origin of the UB and the MM in mouse, and discuss how this impacts on kidney regeneration strategies and furthers our understanding of human development.

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“…Injection of these enriched kidney progenitors into newborn kidneys reduced the risk of teratoma formation. 55 Since these discoveries, more recent work has identified the role of other lineage-specifying factors, such as bone morphogenic protein (BMP)-2, BMP-4, and BMP-7 57 and other small molecules 58 in the establishment of intermediate mesoderm, from which most nephronspecific cell types are derived. Furthermore, the exploration of specific culture conditions and cell markers demonstrates that it is possible to enrich for cells resembling a kidney progenitor state (Table 1).…”

Section: Embryonic Stem Cellsmentioning

confidence: 99%

“…Although limited, methods aimed at efficiently inducing mouse ESCs into renal progenitors and fully differentiated cell types have already been developed (Table 1). [53][54][55][57][58][59] Hijacking the knowledge of such technology to generate mesodermal and renal lineage cells from iPSCs could be possible.…”

Section: Future Challenges and Considerationsmentioning

confidence: 99%

Human Kidney Cell Reprogramming

O'Neill

Ricardo

2013

Journal of the American Society of Nephrology

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The ability to reprogram fully differentiated cells into a pluripotent embryonic state, termed induced pluripotent stem cells (iPSCs), has been met with great excitement. iPSC technology has advanced the fundamental study of disease modeling with the potential for cell-replacement therapy, especially in the neuronal and cardiac fields. However, renal medicine as of yet has not benefited from similar advancements. This review summarizes the unique characteristics of iPSCs and their potential applications for modeling kidney disease. Pioneering such endeavors could yield constructs that recapitulate disease phenotypes, open avenues for more targeted drug development, and potentially serve as replenishable sources for replacement of kidney cells in the setting of human disease.

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Combination of small molecules enhances differentiation of mouse embryonic stem cells into intermediate mesoderm through BMP7-positive cells

Cited by 47 publications

References 35 publications

Rapid and Efficient Differentiation of Human Pluripotent Stem Cells into Intermediate Mesoderm That Forms Tubules Expressing Kidney Proximal Tubular Markers

Rapid and Efficient Differentiation of Human Pluripotent Stem Cells into Intermediate Mesoderm That Forms Tubules Expressing Kidney Proximal Tubular Markers

The origin of the mammalian kidney: implications for recreating the kidney in vitro

Human Kidney Cell Reprogramming

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