scholarly journals Cytokine Directed Chondroblast Trans-Differentiation: JAK Inhibition Facilitates Direct Reprogramming of Fibroblasts to Chondroblasts

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 191
Author(s):  
Perla Cota ◽  
Summer A. Helmi ◽  
Charlie Hsu ◽  
Derrick E. Rancourt
Keyword(s):  
Stem Cells ◽  
Cell Formation ◽  
Induced Pluripotent Stem Cell ◽  
Tumor Formation ◽  
Embryonic Fibroblasts ◽  
Cell State ◽  
Induced Pluripotent ◽  
Pathway Inhibition ◽  
Cartilage Tumor ◽  
Stat Pathway

Osteoarthritis (OA) is a degenerative disease of the hyaline articular cartilage. This disease is progressive and may lead to disability. Researchers proposed many regenerative approaches to treat osteoarthritis, including stem cells. Trans-differentiation of a fully differentiated cell state directly into another different differentiated cell state avoids the disadvantages of fully reprogramming cells to induced pluripotent stem cells (iPSCs) in terms of faster reprogramming of the needed cells. Trans-differentiation also reduces the risk of tumor formation by avoiding the iPSC state. OSKM factors (Oct4, Sox2, Klf4, and cMyc) accompanied by the JAK-STAT pathway inhibition, followed by the introduction of specific differentiation factors, directly reprogrammed mouse embryonic fibroblasts to chondroblasts. Our results showed the absence of intermediate induced pluripotent stem cell formation. The resulting aggregates showed clear hyaline and hypertrophic cartilage. Tumor formation was absent in sub-cutaneous capsules transplanted in SCID mice.

scholarly journals Human germ cell formation in xenotransplants of induced pluripotent stem cells carrying X chromosome aneuploidies

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Antonia A. Dominguez ◽  
H. Rosaria Chiang ◽  
Meena Sukhwani ◽  
Kyle E. Orwig ◽  
Renee A. Reijo Pera
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Induced Pluripotent Stem Cells ◽  
X Chromosome ◽  
Pluripotent Stem Cells ◽  
Cell Formation ◽  
Induced Pluripotent ◽  
Germ Cell Formation

scholarly journals An integration-free, virus-free rhesus macaque induced pluripotent stem cell line (riPSC90) from embryonic fibroblasts

2017 ◽  
Vol 21 ◽  
pp. 5-8 ◽  
Author(s):  
Enrique Sosa ◽  
Rachel Kim ◽  
Ernesto J. Rojas ◽  
Linzi Hosohama ◽  
Jon D. Hennebold ◽  
...  
Keyword(s):  
Stem Cell ◽  
Rhesus Macaque ◽  
Cell Line ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Free Virus ◽  
Stem Cell Line ◽  
Embryonic Fibroblasts ◽  
Induced Pluripotent

scholarly journals Tyrosyl-tRNA synthetase stimulates thrombopoietin-independent hematopoiesis accelerating recovery from thrombocytopenia

2018 ◽  
Vol 115 (35) ◽  
pp. E8228-E8235 ◽  
Author(s):  
Taisuke Kanaji ◽  
My-Nuong Vo ◽  
Sachiko Kanaji ◽  
Alessandro Zarpellon ◽  
Ryan Shapiro ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Formation ◽  
Induced Pluripotent Stem Cell ◽  
Trna Synthetase ◽  
Monocytic Cells ◽  
Formation Continue ◽  
Hematopoietic Stem ◽  
Culture Production ◽  
High Ploidy ◽  
Induced Pluripotent

New mechanisms behind blood cell formation continue to be uncovered, with therapeutic approaches for hematological diseases being of great interest. Here we report an enzyme in protein synthesis, known for cell-based activities beyond translation, is a factor inducing megakaryocyte-biased hematopoiesis, most likely under stress conditions. We show an activated form of tyrosyl-tRNA synthetase (YRSACT), prepared either by rationally designed mutagenesis or alternative splicing, induces expansion of a previously unrecognized high-ploidy Sca-1+ megakaryocyte population capable of accelerating platelet replenishment after depletion. Moreover, YRSACT targets monocytic cells to induce secretion of transacting cytokines that enhance megakaryocyte expansion stimulating the Toll-like receptor/MyD88 pathway. Platelet replenishment by YRSACT is independent of thrombopoietin (TPO), as evidenced by expansion of the megakaryocytes from induced pluripotent stem cell-derived hematopoietic stem cells from a patient deficient in TPO signaling. We suggest megakaryocyte-biased hematopoiesis induced by YRSACT offers new approaches for treating thrombocytopenia, boosting yields from cell-culture production of platelet concentrates for transfusion, and bridging therapy for hematopoietic stem cell transplantation.

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