Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds

Huangfu, Danwei; Maehr, René; Guo, Wenjun; Eijkelenboom, Astrid; Snitow, Melinda; Chen, Alice E.; Melton, Douglas A.

doi:10.1038/nbt1418

Cited by 1,484 publications

(1,289 citation statements)

References 14 publications

Supporting

Mentioning

1,231

Contrasting

Unclassified

Order By: Relevance

“…To this end, several inhibitors of DNA and histone methyltransferase, as well as histone deacetylase (HDAC) inhibitors have been found to dramatically improve reprogramming efficiency (Huangfu et al, 2008a;Shi et al, 2008).…”

Section: Change Of Epigenetic Landscapementioning

confidence: 99%

“…The first compounds used in reprogramming experiments were DNA methyltransferase inhibitor 5′-azacytidine and the HDAC inhibitor valproic acid (VPA), which increased the reprogramming efficiency by five fold and more than a hundred fold respectively (Huangfu et al, 2008a(Huangfu et al, , 2008bMikkelsen et al, 2008). Some small molecules could replace certain reprogramming factors.…”

Section: Chemical Compoundsmentioning

confidence: 99%

See 1 more Smart Citation

Mechanism and methods to induce pluripotency

Wang

2011

Protein Cell

View full text Add to dashboard Cite

Pluripotent stem cells are able to self-renew indefinitely and differentiate into all types of cells in the body. They can thus be an inexhaustible source for future cell transplantation therapy to treat degenerative diseases which currently have no cure. However, non-autologous cells will cause immune rejection. Induced pluripotent stem cell (iPSC) technology can convert somatic cells to the pluripotent state, and therefore offers a solution to this problem. Since the first generation of iPSCs, there has been an explosion of relevant research, from which we have learned much about the genetic networks and epigenetic landscape of pluripotency, as well as how to manipulate genes, epigenetics, and microRNAs to obtain iPSCs. In this review, we focus on the mechanism of cellular reprogramming and current methods to induce pluripotency. We also highlight new problems emerging from iPSCs. Better understanding of the fundamental mechanisms underlying pluripotenty and refining the methodology of iPSC generation will have a significant impact on future development of regenerative medicine.

show abstract

Section: Change Of Epigenetic Landscapementioning

confidence: 99%

Section: Chemical Compoundsmentioning

confidence: 99%

Mechanism and methods to induce pluripotency

Wang

2011

Protein Cell

View full text Add to dashboard Cite

show abstract

“…Barriers to this approach include the use of viral vectors and potentially oncogenic genes, as in the case of iPS [139]. The reprogramming potential of small molecules is already being investigated as an alternative [140,141].…”

Section: Differentiating the Renal Blastemamentioning

confidence: 99%

Stem cell options for kidney disease

Hopkins

Rae

et al. 2008

The Journal of Pathology

View full text Add to dashboard Cite

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...

show abstract

“…In addition, the viral vectors after integration with the host may lead to unexpected genetic disorder (Okita et al 2007;Takahashi et al 2007;Tateishi et al 2008;Yu et al 2009). Therefore, new and improved methods of generating iPS cells, including minimal or no genetic modification are needed (Huangfu et al 2008;Kaji et al 2009;Okita et al 2008;Stadtfeld et al 2008;Woltjen et al 2009;Yu et al 2009;Zhou et al 2009). Tateishi et al (2008) reported that iPS cells derived from human skin fibroblast by retroviral expression of OCT4, SOX2, c-MYC, and KLF4 have the potential to differentiate into insulin-producing islet-like clusters (ILCs).…”

Section: Differentiation Of Induced Pluripotent Stem Cellsmentioning

confidence: 99%

Differentiation of Stem Cells into Insulin-Producing Cells: Current Status and Challenges

Pokrywczyńska

Krzyzanowska

Jundziłł

et al. 2013

Arch. Immunol. Ther. Exp.

View full text Add to dashboard Cite

Diabetes mellitus is one of the most serious public health challenges of the twenty-first century. Allogenic islet transplantation is an efficient therapy for type 1 diabetes. However, immune rejection, side effects of immunosuppressive treatment as well as lack of sufficient donor organs limits its potential. In recent years, several promising approaches for generation of new pancreatic b cells have been developed. This review provides an overview of current status of pancreatic and extra-pancreatic stem cells differentiation into insulin-producing cells and the possible application of these cells for diabetes treatment. The PubMed database was searched for English language articles published between 2001 and 2012, using the keyword combinations: diabetes mellitus, differentiation, insulin-producing cells, stem cells.

show abstract

Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds

Cited by 1,484 publications

References 14 publications

Mechanism and methods to induce pluripotency

Mechanism and methods to induce pluripotency

Stem cell options for kidney disease

Differentiation of Stem Cells into Insulin-Producing Cells: Current Status and Challenges

Contact Info

Product

Resources

About