+ Most Popular
Cunninghamia lanceolata plantations in China
Mammalian lairs in paleo ecological studies and palynology
Studies on technological possibilities in utilization of anhydrous milk fat for production of recombined butter-like products
Should right-sided fibroelastomas be operated upon?
Large esophageal lipoma
Apoptosis in the mammalian thymus during normal histogenesis and under various in vitro and in vivo experimental conditions
Poissons characoides nouveaux ou non signales de l'Ilha do Bananal, Bresil
Desensitizing efficacy of Colgate Sensitive Maximum Strength and Fresh Mint Sensodyne dentifrices
Administration of fluid by subcutaneous infusion: revival of a forgotten method
Tundra mosquito control - an impossible dream?
Schizophrenia for primary care providers: how to contribute to the care of a vulnerable patient population
Geochemical pattern analysis; method of describing the Southeastern limestone regional aquifer system
Incidence of low birth weights in a hospital of Mexico City
Graded management intensity of grassland systems for enhancing floristic diversity
Microbiology and biochemistry of cheese and fermented milk
The ember tetra: a new pygmy characid tetra from the Rio das Mortes, Brazil, Hyphessobrycon amandae sp. n. (Pisces, Characoidei)
Risk factors of contrast-induced nephropathy in patients after coronary artery intervention
Renovation of onsite domestic wastewater in a poorly drained soil
Observations of the propagation velocity and formation mechanism of burst fractures caused by gunshot
Systolic blood pressure in a population of infants in the first year of life: the Brompton study
Haematological studies in rats fed with metanil yellow
Studies on pasteurellosis. I. A new species of Pasteurella encountered in chronic fowl cholera
Dormancy breaking and germination of Acacia salicina Lindl. seeds
therapy of lupus nephritis. a two-year prospective study

Induction of alternative fate other than default neuronal fate of embryonic stem cells in a membrane-based two-chambered microbioreactor by cell-secreted BMP4

Induction of alternative fate other than default neuronal fate of embryonic stem cells in a membrane-based two-chambered microbioreactor by cell-secreted BMP4

Biomicrofluidics 6(1): 14117-1411713

ISSN/ISBN: 1932-1058

PMID: 22662099

DOI: 10.1063/1.3693590

Cell-secreted soluble factor signaling in a diffusion dominant microenvironment plays an important role on early stage differentiation of pluripotent stem cells invivo. In this study, we utilized a membrane-based two-chambered microbioreactor (MB) to differentiate mouse embryonic stem cells (mESCs) in a diffusion dominant microenvironment of the top chamber while providing enough nutrient through the bottom chamber. Speculating that accumulated FGF4 in the small top chamber will augment neuronal differentiation in the MB culture, we first differentiated mESCs for 8 days by using a chemically optimized culture medium for neuronal induction. However, comparison of cellular morphology and expression of neuronal markers in the MB with that in the 6-well plate (6WP) indicated relatively lower neuronal differentiation in the MB culture. Therefore, to investigate whether microenvironment in the MB facilitates non-neuronal differentiation, we differentiated mESCs for 8 days by using chemically defined basal medium. In this case, differentiated cell morphology differed markedly between the MB and 6WP cultures: epithelial sheet-like morphology in the MB, whereas rosette morphology in the 6WP. Expression of markers from the three germ layers indicated lower neuronal but higher meso- and endo-dermal differentiation of mESCs in the MB than the 6WP culture. Moreover, among various cell-secreted soluble factors, BMP4 expression was remarkably upregulated in the MB culture. Inhibition of BMP4 signaling demonstrated that enhanced effect of upregulated BMP4 was responsible for the prominent meso- and endo-dermal differentiation in the MB. However, in the 6WP, downregulated BMP4 had a minimal influence on the differentiation behavior. Our study demonstrated utilization of a microbioreactor to modulate the effect of cell-secreted soluble factors by autoregulation and thereby inducing alternative self-capability of mESCs. Understanding and implementation of autoregulation of soluble factors similar to this study will lead to the development of robust culture systems to control ESC behavior.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 053820877

Download citation: RISBibTeXText

Related references

Direct neural fate specification from embryonic stem cells: A primitive mammalian neural stem cell stage acquired through a default mechanism. Neuron 30(1): 65-78, 2001

SMAD7 directly converts human embryonic stem cells to telencephalic fate by a default mechanism. Stem Cells 31(1): 35-47, 2013

Early neuronal and glial fate restriction of embryonic neural stem cells. Journal of Neuroscience: the Official Journal of the Society for Neuroscience 28(10): 2551-2562, 2008

GROα regulates human embryonic stem cell self-renewal or adoption of a neuronal fate. Differentiation; Research in Biological Diversity 81(4): 222-232, 2011

Constraining the Pluripotent Fate of Human Embryonic Stem Cells for Tissue Engineering and Cell Therapy - The Turning Point of Cell-Based Regenerative Medicine. British Biotechnology Journal 3(4): 424-457, 2013

Substrate topography and size determine the fate of human embryonic stem cells to neuronal or glial lineage. Acta Biomaterialia 9(1): 4535-4545, 2013

A Brn2-Zic1 axis specifies the neuronal fate of retinoic-acid-treated embryonic stem cells. Journal of Cell Science 128(13): 2303-2318, 2015

Neuronal vs. glial fate of embryonic stem cell-derived neural progenitors (ES-NPs) is determined by FGF2/EGF during proliferation. Journal of Molecular Neuroscience: Mn 42(1): 17-27, 2010

DNA damage in embryonic neural stem cell determines FTLDs' fate via early-stage neuronal necrosis. Life Science Alliance 4(7), 2021

Epidermal stem cell fate: what can we learn from embryonic stem cells?. Cell and Tissue Research 331(1): 103-107, 2008

Early cell fate decisions of human embryonic stem cells and mouse epiblast stem cells are controlled by the same signalling pathways. Plos one 4(6): E6082, 2009

Zfhx1b induces a definitive neural stem cell fate in mouse embryonic stem cells. Stem Cells and Development 21(15): 2838-2851, 2012

Embryonic Stem Cells Assume a Primitive Neural Stem Cell Fate in the Absence of Extrinsic Influences. The Journal of Cell Biology 172(1): 79-90, 2006

Embryonic stem cells assume a primitive neural stem cell fate in the absence of extrinsic influences. Journal of Cell Biology 172(1): 79-90, 2006

Human embryonic stem cells and cardiac cell fate. Journal of Cellular Physiology 218(3): 455-459, 2009