Leukemia inhibitory factor (LIF) concentration modulates embryonic stem cell self-renewal and differentiation independently of proliferation

Zandstra, Peter W.; Han, Le; Daley, George Q.; Griffith, Linda G.; Lauffenburger, D. A.

doi:10.1002/1097-0290(20000920)69:6<607::aid-bit4>3.0.co;2-f

Cited by 83 publications

(54 citation statements)

References 54 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By dividing the total number of EBs per 96-well plate by the number of input ES cells, we determined that individual ES cells could form EBs with an overall e ciency of at least 2 2 2 2 2 2 2 2 2 2 42 9% (Table I). In a separate set of experiments, we determined that 78?9% of our starting cell population was ES cells based on Ecadherin and SSEA-1 expression (data not shown, [Zandstra, et al 2000]). We therefore estimated that the remaining 22 9% was composed of STO feeder cells or di erentiated cells.…”

Section: Individual Es Cells Can Form Ebsmentioning

confidence: 99%

Efficiency of embryoid body formation and hematopoietic development from embryonic stem cells in different culture systems

Dang

Kyba

Perlingeiro

et al. 2002

Biotech & Bioengineering

316

253

View full text Add to dashboard Cite

Embryonic stem (ES) cells have tremendous potential as a cell source for cell-based therapies. Realization of that potential will depend on our ability to understand and manipulate the factors that in¯uence cell fate decisions and to develop scalable methods of cell production. We compared four standard ES cell differentiation culture systems by measuring aspects of embryoid body (EB) formation ef®ciency and cell proliferation, and by tracking development of a speci®c differentiated tissue typeÐbloodÐusing functional (colony-forming cell) and phenotypic (Flk-1 and CD34 expression) assays. We report that individual murine 1 1 1 1 1 1 1 1 1 1 ES cells form EBs with an ef®ciency of 2 2 2 2 2 2 2 2 2 2 42 9%, but this value is rarely obtained because of EB aggregationÐa process whereby two or more individual ES cells or EBs fuse to form a single, larger cell aggregate. Regardless of whether EBs were generated from a single ES cell in methylcellulose or liquid suspension culture, or aggregates of ES cells in hanging drop culture, they grew to a similar maximum cell number of 28,000 9,000 cells per EB. Among the three methods for EB generation in suspension culture there were no differences in the kinetics or frequency of hematopoietic development. Thus, initiating EBs with a single ES cell and preventing EB aggregation should allow for maximum yield of differentiated cells in the EB system. EB differentiation cultures were also compared to attached differentiation culture using the same outputs. Attached colonies were not similarly limited in cell number; however, hematopoietic development in attached culture was impaired. The percentage of early Flk-1 and CD34 expressing cells was dramatically lower than in EBs cultured in suspension, whereas hematopoietic colony formation was almost completely inhibited. These results provide a foundation for development of ef®cient, scalable bioprocesses for ES cell differentiation, and inform novel methods for the production of hematopoietic tissues.

show abstract

Section: Individual Es Cells Can Form Ebsmentioning

confidence: 99%

Efficiency of embryoid body formation and hematopoietic development from embryonic stem cells in different culture systems

Dang

Kyba

Perlingeiro

et al. 2002

Biotech & Bioengineering

316

253

View full text Add to dashboard Cite

show abstract

“…However, the LIF-induced STAT3 activation is not coupled to proliferation since inhibition of STAT3 activity by using the JAK2 inhibitor AG490 did not affect LIF-induced proliferation of P19 EC cells. In mouse ES cells, it has been demonstrated that ES cell growth is independent of the LIF concentration [36]. Further experiments indicated that similar proportions of ES cells were in the G2, M, or S phase, regardless of whether the cultures were supplemented with 500 pM LIF or 1 g/ml ␣-LIF to inhibit low levels of LIF present in serum [36].…”

Section: Figmentioning

confidence: 99%

“…In mouse ES cells, it has been demonstrated that ES cell growth is independent of the LIF concentration [36]. Further experiments indicated that similar proportions of ES cells were in the G2, M, or S phase, regardless of whether the cultures were supplemented with 500 pM LIF or 1 g/ml ␣-LIF to inhibit low levels of LIF present in serum [36]. However, the LIF concentration appeared to be important in determining the probability of an ES cell undergoing a selfrenewal versus a differentiation division.…”

Section: Figmentioning

confidence: 99%

LIF-Induced STAT3 Signaling in Murine versus Human Embryonal Carcinoma (EC) Cells

Schuringa

Schaaf

Vellenga³

et al. 2002

Experimental Cell Research

View full text Add to dashboard Cite

“…LIF is a key neuropoietic cytokine [6] and regulator of stem cells [7]. Comparative gene array of graft-''tolerant'' spleen cells versus graft-''rejected'' splenocytes identified axotrophin, a newly characterised stem cell gene [9], as being specifically increased in tolerance [8]. Here, we ask if axotrophin plays a role in immune regulation and show not only that axotrophin plays a critical role in the regulation of T lymphocytes, but also that axotrophin is functionally linked to the regulation of LIF.…”

Section: Introductionmentioning

confidence: 99%

Leukaemia inhibitory factor (LIF) is functionally linked to axotrophin and both LIF and axotrophin are linked to regulatory immune tolerance

et al. 2004

View full text Add to dashboard Cite

Axotrophin (axot) is a newly characterised stem cell gene and mice that lack axotrophin are viable and fertile, but show premature neural degeneration and defective development of the corpus callosum. By comparing axot +/+ , axot +/À and axot À/À littermates, we now show that axotrophin is also involved in immune regulation. Both T cell proliferation and T cell-derived leukaemia inhibitory factor (LIF) were suppressed by axotrophin in a gene-dose-dependent manner. Moreover, a role for axotrophin in the feedback regulation of LIF is implicated. This is the first evidence that fate determination mediated by LIF maybe qualified by axotrophin.

show abstract

Leukemia inhibitory factor (LIF) concentration modulates embryonic stem cell self-renewal and differentiation independently of proliferation

Cited by 83 publications

References 54 publications

Efficiency of embryoid body formation and hematopoietic development from embryonic stem cells in different culture systems

Efficiency of embryoid body formation and hematopoietic development from embryonic stem cells in different culture systems

LIF-Induced STAT3 Signaling in Murine versus Human Embryonal Carcinoma (EC) Cells

Leukaemia inhibitory factor (LIF) is functionally linked to axotrophin and both LIF and axotrophin are linked to regulatory immune tolerance

Contact Info

Product

Resources

About