scholarly journals In Vitro Pluripotent Stem Cell Differentiation to Hepatocyte Ceases Further Maturation at an Equivalent Stage of E15 in Mouse Embryonic Liver Development

2018 ◽  
Vol 27 (13) ◽  
pp. 910-921 ◽  
Author(s):  
Ravali Raju ◽  
David Chau ◽  
Tineke Notelaers ◽  
Chad L. Myers ◽  
Catherine M. Verfaillie ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Pluripotent Stem Cell ◽  
Stem Cell Differentiation ◽  
Liver Development ◽  
Embryonic Liver

scholarly journals Ectopic HOXB4 Expression Expands the Pool of Hemogenic Endothelium-Initiating Progenitor Cells during Pluripotent Stem Cell Differentiation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3496-3496
Author(s):  
Nadine Teichweyde ◽  
Lara Kasperidus ◽  
Peter A Horn ◽  
Hannes Klump
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Pluripotent Stem Cell ◽  
Stem Cell Differentiation ◽  
Great Promise ◽  
Hemogenic Endothelium ◽  
Hematopoietic Development

Abstract Generation of hematopoietic stem cells (HSCs) from pluripotent stem cells, in vitro, holds great promise for future somatic gene and cell therapy. So far, HSCs capable of long-term multilineage reconstitution in mice have only been obtained when the homeodomain transcription factor HOXB4 was ectopically expressed during pluripotent stem cell differentiation (Kyba et al. Cell 109(1): 29-37, 2002; Pilat et al. Proc Natl Acad Sci USA 102(34): 12101-12106, 2005; Lesinski et al. Stem Cells Transl Med 1(8): 581-591, 2012). However, the primary "target" cell of HOXB4 during hematopoietic development, in vitro, is not yet known. Its identification is a prerequisite for unambiguously identifying the molecular circuits driving HSC development, at least in vitro. To pin down this cell, we retrovirally expressed HOXB4 or a Tamoxifen-inducible HOXB4-ERT2 fusion protein in different reporter and knock-out mouse embryonic stem cell (ESC) lines. For these experiments, ESCs were differentiated for 6 days as embryoid bodies (EBs), dissociated and subsequently cocultured on OP9 stroma cells in medium supplemented with 100 ng/ml mSCF, 40 ng/ml mTPO, 100 ng/ml hFlt3L and 40 ng/ml hVEGF (STFV) for further 3 days. Use of a Runx1(-/-) ESC-line containing a doxycycline-inducible Runx1 coding sequence (“iRunx1”; kindly provided by G. Lacaud, Manchester) uncovered that HOXB4 acts during formation of the hemogenic endothelium (HE) from which HSCs arise. Without Runx1 induction, which arrests hematopoietic development at the HE-stage, ectopic HOXB4 expression mediated an approximately 30-fold increase in the number of circular endothelial, bona fide HE-sheets being Flk1+VE-Cadherin+Tie2+ (mean values: control: 11+/-4.8 n=7; HOXB4: 301+/-47 n=7; P<0.0001, unpaired, 2-sided Student´s t-test) and expressing Sox17 and Lmo2. This observation suggested an expansion of HE progenitors, detectable from day 5 of EB differentiation on. Determination of their frequencies within the VE-Cadherin+ population revealed a HOXB4-mediated increase from 1:360 cells (control) up to 1:15 cells (HOXB4; 95% C.I. = 1:12-1:21). After additional Runx1 induction, the endothelial cells morphologically underwent an Endothelial-to-Hematopoietic Transition (EHT) as verified at the single cell level by time-lapse microscopy. Concomitantly, they upregulated transcription of Gfi1, Gfi1b and Pu.1, initiated surface expression of the pan-hematopoietic marker CD45 and generated hematopoietic colony forming cells (CFC), thus proving their identity as real hemogenic endothelial cells. Taken together, our results strongly suggest that HOXB4 first and foremost promotes hematopoiesis by substantially increasing the number of hemogenic endothelium progenitors during mouse pluripotent stem cell differentiation. Disclosures No relevant conflicts of interest to declare.

scholarly journals Chromobox Protein Homolog 3 Is Essential for Stem Cell Differentiation to Smooth Muscles In Vitro and in Embryonic Arteriogenesis

2011 ◽  
Vol 31 (8) ◽  
pp. 1842-1852 ◽  
Author(s):  
Qingzhong Xiao ◽  
Gang Wang ◽  
Xiaoke Yin ◽  
Zhenling Luo ◽  
Andriani Margariti ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Smooth Muscles ◽  
Stem Cell Differentiation

scholarly journals Human adipose stem cell differentiation is highly affected by cancer cells both in vitro and in vivo: implication for autologous fat grafting

2017 ◽  
Vol 8 (1) ◽  
pp. e2568-e2568 ◽  
Author(s):  
Francesca Paino ◽  
Marcella La Noce ◽  
Diego Di Nucci ◽  
Giovanni Francesco Nicoletti ◽  
Rosa Salzillo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Stem Cell Differentiation ◽  
Fat Grafting ◽  
Adipose Stem Cell ◽  
Autologous Fat Grafting ◽  
Autologous Fat ◽  
Human Adipose Stem Cell

scholarly journals Developmental Pathways Pervade Stem Cell Responses to Evolving Extracellular Matrices of 3D Bioprinted Microenvironments

2018 ◽  
Vol 2018 ◽  
pp. 1-15
Author(s):  
Quyen A. Tran ◽  
Visar Ajeti ◽  
Brian T. Freeman ◽  
Paul J. Campagnola ◽  
Brenda M. Ogle
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Early Time ◽  
Stem Cell Differentiation ◽  
Model Systems ◽  
Ecm Remodeling ◽  
Time Points ◽  
3D Microenvironment

Developmental studies and 3D in vitro model systems show that the production and engagement of extracellular matrix (ECM) often precede stem cell differentiation. Yet, unclear is how the ECM triggers signaling events in sequence to accommodate multistep process characteristic of differentiation. Here, we employ transcriptome profiling and advanced imaging to delineate the specificity of ECM engagement to particular differentiation pathways and to determine whether specificity in this context is a function of long-term ECM remodeling. To this end, human mesenchymal stem cells (hMSCs) were cultured in 3D bioprinted prisms created from ECM proteins and associated controls. We found that exogenous ECM provided in 3D microenvironments at early time points impacts on the composition of microenvironments at later time points and that each evolving 3D microenvironment is uniquely poised to promote stem cell differentiation. Moreover, 2D cultures undergo minimal ECM remodeling and are ill-equipped to stimulate pathways associated with development.

scholarly journals A bioengineering approach to Schlemm's canal-like stem cell differentiation for in vitro glaucoma drug screening

2020 ◽  
Vol 105 ◽  
pp. 203-213 ◽  
Author(s):  
Yangzi Isabel Tian ◽  
Xulang Zhang ◽  
Karen Torrejon ◽  
John Danias ◽  
Sofya Gindina ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Drug Screening ◽  
Stem Cell Differentiation ◽  
Schlemm’S Canal ◽  
Schlemm's Canal
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