Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells

Schuldiner, Maya; Yanuka, Ofra; Itskovitz‐Eldor, Joseph; Melton, Douglas A.; Benvenisty, Nissim

doi:10.1073/pnas.97.21.11307

Cited by 1,026 publications

(681 citation statements)

References 22 publications

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“…This is somehow in contrast with the fact that in developing embryos, HNF-6 is expressed in a lineage-restricted manner [17]. However, several lineage-restricted factors, which include HNF-1α, HNF-1β and PDX-1 [29,34,35], are known to be expressed in undifferentiated ES cells and we show here that this is also the case for NGN-3. More importantly, we found that HNF-6 is also expressed in the outer layer of the EBs, which is consistent with the known expression of HNF-6 in the yolk sac [36].…”

Section: Discussioncontrasting

confidence: 58%

HNF-6-independent differentiation of mouse embryonic stem cells into insulin-producing cells

Houard¹,

Rousseau²,

Lemaigre³

2003

Diabetologia

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Aims/hypothesis. Embryonic stem cells, when grown as embryoid bodies, spontaneously generate insulinproducing cells which could be used in therapy of diabetes mellitus, provided that their selection and differentiation are optimized. To achieve such optimization, one needs to know whether the differentiation of cells in embryoid bodies mimicks that of pancreatic beta cells in embryos. To address this question we verified if the differentiation of the insulin-producing cells in embryoid bodies requires Hepatocyte Nuclear Factor-6 (HNF-6), a transcription factor known to control pancreatic endocrine differentiation in embryos. Methods. We generated mouse Hnf6−/− embryonic stem cells and grew them as embryoid bodies. The expression of HNF-6, insulin, and transcription factors that are regulated by HNF-6 in developing pancreas was compared in wild-type and Hnf6−/− embryoid bodies. Results.No difference was observed in the expression of insulin between wild-type and Hnf6−/− embryoid bodies. In both cases insulin was expressed in the outer layer of cells, which is similar to the visceral endoderm. In wild-type embryoid bodies HNF-6 was transiently expressed in the outer layer of cells, but was not co-expressed with insulin. The expression of genes that are targets of HNF-6 in developing pancreas was unaffected in Hnf6−/− embryoid bodies. Conclusion/interpretation. In contrast to the development of pancreatic beta cells, the differentiation of insulin-producing cells in embryoid bodies did not require HNF-6. Thus, the differentiation mechanism of insulin-producing cells in embryoid bodies differs from that of the beta cells and it is likely to resemble that of insulin-producing cells in the visceral endoderm. [Diabetologia (2003) 46:378-385]

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Section: Discussioncontrasting

confidence: 58%

HNF-6-independent differentiation of mouse embryonic stem cells into insulin-producing cells

Houard¹,

Rousseau²,

Lemaigre³

2003

Diabetologia

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“…In addition to this self-renewal ability, hESCs differentiate both in vivo and in vitro, generating representatives of all three embryonic germ layers, including neural progenitors, cardiomyocytes, trophoblast cells, endothelial cells, hematopoietic lineages, hepatocyte-like cells, osteoblasts, and insulin-expressing cells [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Because of these fundamental characteristics, hESCs hold promise for cell-based therapies for degenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

Basic Fibroblast Growth Factor Supports Undifferentiated Human Embryonic Stem Cell Growth Without Conditioned Medium

et al. 2005

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Previous studies have shown that prolonged propagation of undifferentiated human embryonic stem cells (hESCs) requires conditioned medium from mouse embryonic feeders (MEF-CM) as well as matrix components. Because hESCs express growth factor receptors, including those for basic fibroblast growth factor (bFGF), stem cell factor (SCF), and fetal liver tyrosine kinase-3 ligand (Flt3L), we evaluated these and other growth factors for their ability to maintain undifferentiated hESCs in the absence of conditioned medium. We found cultures maintained in bFGF alone or in combination with other factors showed characteristics similar to MEF-CM control cultures, including morphology, surface marker and transcription factor expression, telomerase activity, differentiation, and karyotypic stability. In contrast, cells in media containing Flt-3L, thrombopoietin, and SCF, individually or in combination, showed almost complete differentiation after 6 weeks in culture. These data demonstrate that hESCs can be maintained in nonconditioned medium using growth factors. 2005;23:315-323 Stem Cells

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“…See, for instances, the papers of Heo et al [20], Eiselleova et al [21], Chung et al [22], and Schuldiner et al [23]. More generally, other conditions such as the level of oxygen, or of nutrients such as glucose, can also affect the growth of stem cells, as demonstrated in works such as [24,25,26].…”

Section: Modeling Proliferative Index Of Mesenchymal Stem Cellsmentioning

confidence: 99%

Mathematical modeling of stem cell proliferation

Tabatabai

Bursac

Eby

et al. 2010

Med Biol Eng Comput

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Abstract.The mathematical models prevalently used to represent stem cell proliferation do not have the level of accuracy that might be desired. The hyperbolastic growth models promise a greater degree of precision in representing data of stem cell proliferation. The hyperbolastic growth model H3 is applied to experimental data in both embryonic stem cells and adult mesenchymal stem cells. In the embryonic stem cells the results are compared with other popular models, including the Deasy model, which is used prevalently for stem cell growth. In the case of modelling adult mesenchymal stem cells, H3 is also successfully applied to describe the proliferative index. We demonstrated that H3 can accurately represent the dynamics of stem cell proliferation for both embryonic and adult mesenchymnal stem cells. We also recognize the importance of additional factors, such as cytokines, in determining the rate of growth. We propose the question of how to extend H3 to a multivariable model that can include the influence of growth factors.

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Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells

Cited by 1,026 publications

References 22 publications

HNF-6-independent differentiation of mouse embryonic stem cells into insulin-producing cells

HNF-6-independent differentiation of mouse embryonic stem cells into insulin-producing cells

Basic Fibroblast Growth Factor Supports Undifferentiated Human Embryonic Stem Cell Growth Without Conditioned Medium

Mathematical modeling of stem cell proliferation

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