Abstract:
:Significant efforts have been directed to understanding the factors that influence the lineage commitment of stem cells. This paper demonstrates that cell shape, independent of soluble factors, has a strong influence on the differentiation of human mesenchymal stem cells (MSCs) from bone marrow. When exposed to competing soluble differentiation signals, cells cultured in rectangles with increasing aspect ratio and in shapes with pentagonal symmetry but with different subcellular curvature-and with each occupying the same area-display different adipogenesis and osteogenesis profiles. The results reveal that geometric features that increase actomyosin contractility promote osteogenesis and are consistent with in vivo characteristics of the microenvironment of the differentiated cells. Cytoskeletal-disrupting pharmacological agents modulate shape-based trends in lineage commitment verifying the critical role of focal adhesion and myosin-generated contractility during differentiation. Microarray analysis and pathway inhibition studies suggest that contractile cells promote osteogenesis by enhancing c-Jun N-terminal kinase (JNK) and extracellular related kinase (ERK1/2) activation in conjunction with elevated wingless-type (Wnt) signaling. Taken together, this work points to the role that geometric shape cues can play in orchestrating the mechanochemical signals and paracrine/autocrine factors that can direct MSCs to appropriate fates.
journal_name
Proc Natl Acad Sci U S Aauthors
Kilian KA,Bugarija B,Lahn BT,Mrksich Mdoi
10.1073/pnas.0903269107subject
Has Abstractpub_date
2010-03-16 00:00:00pages
4872-7issue
11eissn
0027-8424issn
1091-6490pii
0903269107journal_volume
107pub_type
杂志文章abstract::Genetic manipulation of nitrogenase and key glutamate-forming enzymes can provide mutants that excrete fixed N2 as NH4+. A derepressed N2 fxation mutant (SK-24) has been isolated , which excretes up to 20.2 mumol of fixed N2 as NH4+ per mg of cell protein in 24 hr at room temperature. Biochemical analysis shows that t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.72.1.136
更新日期:1975-01-01 00:00:00
abstract::Studies of biotic remains of polar ice caps have been limited to morphological identification of plant pollen and spores. By using sensitive molecular techniques, we now demonstrate a much greater range of detectable organisms; from 2000- and 4000-year-old ice-core samples, we obtained and characterized 120 clones tha...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.14.8017
更新日期:1999-07-06 00:00:00
abstract::Throughout time, operational laws and concepts from complex systems have been employed to quantitatively model important aspects and interactions in nature and society. Nevertheless, it remains enigmatic and challenging, yet inspiring, to predict the actual interdependencies that comprise the structure of such systems...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2020-04-07 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2017-09-19 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:1981-07-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2004-11-09 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2020-05-26 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
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更新日期:2019-06-18 00:00:00
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更新日期:1976-04-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2018-07-03 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:1976-10-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:1993-08-15 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2014-01-07 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2017-12-26 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0904100106
更新日期:2009-09-15 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2012-07-17 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2016-07-19 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2017-12-19 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2016-12-27 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2016-02-23 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:1995-12-05 00:00:00
abstract::Navigation, the ability to reach desired goal locations, is critical for animals and humans. Animal navigation has been studied extensively in birds, insects, and some marine vertebrates and invertebrates, yet we are still far from elucidating the underlying mechanisms in other taxonomic groups, especially mammals. He...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2011-09-13 00:00:00
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更新日期:1996-05-14 00:00:00