Metabolic programming of nephron progenitor cell fate

2020 ◽  
Author(s):  
Giovane G Tortelote ◽  
Mariel Colón-Leyva ◽  
Zubaida Saifudeen
Keyword(s):  
Cell Fate ◽  
Progenitor Cell ◽  
Metabolic Programming ◽  
Nephron Progenitor

scholarly journals Disparate levels of beta-catenin activity determine nephron progenitor cell fate

2018 ◽  
Vol 440 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Harini Ramalingam ◽  
Alicia R. Fessler ◽  
Amrita Das ◽  
M. Todd Valerius ◽  
Jeannine Basta ◽  
...  
Keyword(s):  
Cell Fate ◽  
Progenitor Cell ◽  
Beta Catenin ◽  
Nephron Progenitor

Interferon β-1b directly modulates human neural stem/progenitor cell fate

2011 ◽  
Vol 1413 ◽  
pp. 1-8 ◽  
Author(s):  
W. Tristram Arscott ◽  
John Soltys ◽  
Julia Knight ◽  
Yang Mao-Draayer
Keyword(s):  
Cell Fate ◽  
Progenitor Cell ◽  
Interferon Β

scholarly journals Phosphorylation state of the histone variant H2A.X controls human stem and progenitor cell fate decisions

Cell Reports ◽  
2021 ◽  
Vol 34 (10) ◽  
pp. 108818
Author(s):  
Luca Orlando ◽  
Borko Tanasijevic ◽  
Mio Nakanishi ◽  
Jennifer C. Reid ◽  
Juan L. García-Rodríguez ◽  
...  
Keyword(s):  
Cell Fate ◽  
Progenitor Cell ◽  
Histone Variant ◽  
Phosphorylation State ◽  
Cell Fate Decisions

Abstract 340: Short Telomeres Induce Autophagy and Modulate Cardiac Progenitor Cell Fate

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Nirmala Hariharan ◽  
Collin Matsumoto ◽  
Jacqueline Emathinger ◽  
Saba Daneshpooy ◽  
Minyoung Shin ◽  
...  
Keyword(s):  
Cell Fate ◽  
Progenitor Cell ◽  
Smooth Muscle Actin ◽  
Wild Mouse ◽  
Degradation Process ◽  
Mouse Strains ◽  
Therapeutic Effects ◽  
Cardiac Progenitor Cell ◽  
Altered Cell ◽  
The Impact

Aging severely limits myocardial regeneration. Delineating the impact of age-associated factors such as short telomeres is critical to enhance the regenerative potential of cardiac progenitor cells (CPCs). We hypothesize that short telomeres induce autophagy and elicit the age-associated change in cardiac progenitor cell fate. We compared mouse strains with different telomere lengths (TL) for phenotypic characteristics of aging and also isolated CPCs from them. Naturally occurring wild mouse strain Mus musculus castaneus (CAST) possessing short telomeres (TL:18Kb) exhibits early cardiac aging with diastolic dysfunction, hypertrophy, fibrosis and increase in senescence markers p53 and p16, as compared to common lab strains FVB (TL:75Kb) and C57 (TL:50Kb). CAST CPCs with short TLs have altered cell fate as characterized by slower proliferation (p<0.01); increased senescence identified by beta-galactosidase activity (p<0.05); increased basal commitment as determined by expression of lineage markers smooth muscle actin, Tie2, and sarcomeric actinin (16.6, 1.7 and 1.75, p<0.05); as well as loss of quiescence marker expression. Consistent findings of altered cell fate are also evident in old CPCs isolated from aged mice with significantly shorter TLs. Cell fate changes occurring downstream from short TL are at least partially p53 dependent, as p53 inhibition rescues the irreversible cell cycle arrest observed in CAST CPCs. Mechanistically, short TLs induce autophagy, a catabolic protein degradation process. Autophagy flux is increased in CAST CPCs as evidenced by increased LC3 (p<0.05), reduced p62 expression (-52%, p<0.05) and increased accumulation of autophagic puncta. Pharmacological inhibition of autophagosome formation, but not autolysosome formation reverses the cell fate to a more youthful phenotype. Overall the data suggests that short TLs activate autophagy to accommodate cell fate changes that tip the equilibrium away from quiescence and proliferation into differentiation and senescence, leading to age-associated exhaustion of CPCs. The study provides the mechanistic basis underlying age-associated cell fate changes that will enable identification of molecular strategies to enhance the therapeutic effects of aged CPCs.

scholarly journals Metabolic programming of mesenchymal stromal cells by oxygen tension directs chondrogenic cell fate

2014 ◽  
Vol 111 (38) ◽  
pp. 13954-13959 ◽  
Author(s):  
J. Leijten ◽  
N. Georgi ◽  
L. Moreira Teixeira ◽  
C. A. van Blitterswijk ◽  
J. N. Post ◽  
...  
Keyword(s):  
Cell Fate ◽  
Oxygen Tension ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Metabolic Programming

Abstract 356: Krueppel-Like Factor 15 Regulates Wnt/β-Catenin Transcription and Controls Cardiac Progenitor Cell Fate in the Postnatal Heart

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Claudia Noack ◽  
Maria P Zafiriou ◽  
Anke Renger ◽  
Hans J Schaeffer ◽  
Martin W Bergmann ◽  
...  
Keyword(s):  
Cell Fate ◽  
Transcriptional Activation ◽  
Progenitor Cell ◽  
Cellular Localization ◽  
Target Genes ◽  
Critical Role ◽  
Isolated Cells ◽  
Cardiac Progenitor Cell

Wnt/β-catenin signaling controls adult heart remodeling partly by regulating cardiac progenitor cell (CPC) differentiation. We now identified and characterized a novel cardiac interaction of the transcription factor Krueppel-like factor 15 (KLF15) with the Wnt/β-catenin signaling on adult CPCs. In vitro mutation, reporter gene assays and co-localization studies revealed that KLF15 requires two distinct domains for nuclear localization and for repression of β-catenin-mediated transcription. KLF15 had no effect on β-catenin stability or cellular localization, but interacted with its co-factor TCF4, which is required for activation of β-catenin target gene expression. Moreover, increased TCF4 ubiquitination was induced by KLF15. In line with this finding we found KLF15 to interact with the Nemo-like kinase, which was shown to phosphorylate and target TCF4 for degradation. In vivo analyses of adult Klf15 functional knock-out (KO) vs. wild-type (WT) mice showed a cardiac β-catenin-mediated transcriptional activation and reduced TCF4 degradation along with cardiac dysfunction assessed by echocardiography (n=10). FACS analysis of the CPC enriched-population of KO vs. WT mice revealed a significant reduction of cardiogenic-committed precursors identified as Sca1+/αMHC+ (0.8±0.2% vs. 1.8±0.1%) and Tbx5+ (3.5±0.3% vs. 5.2±0.5%). In contrast, endothelial Sca1+/CD31+ cells were significantly higher in KO mice (11.3±0.4% vs. 8.6±0.4%; n≥9). In addition, Sca1+ isolated cells of Klf15 KO showed increased RNA expression of endothelial markers von Willebrand Factor, CD105, and Flk1 along with upregulation of β-catenin target genes. CPCs co-cultured on adult fibroblasts resulted in increased endothelial Flk1 cells and reduction of αMHC and Hand1 cardiogenic cells in KO vs. WT CPCs (n=9). Treating these co-cultures with Quercetin, an inhibitor of nuclear β-catenin, resulted in partial rescue of the observed phenotype. This study uncovers a critical role of KLF15 for the maintenance of cardiac tissue homeostasis. Via inhibition of β-catenin transcription, KLF15 controls cardiomyogenic cell fate similar to embryonic cardiogenesis. This knowledge may provide a tool for activation of endogenous CPCs in the postnatal heart.

Extrinsic and intrinsic factors control the genesis of amacrine and cone cells in the rat retina

Development ◽  
1999 ◽  
Vol 126 (3) ◽  
pp. 555-566 ◽  
Author(s):  
M.J. Belliveau ◽  
C.L. Cepko
Keyword(s):  
Progenitor Cells ◽  
Cell Fate ◽  
Progenitor Cell ◽  
Amacrine Cell ◽  
Amacrine Cells ◽  
Environment Change ◽  
Rat Retina ◽  
Cell Fate Decisions ◽  
Cone Cells ◽  
Postnatal Environment

The seven major classes of cells of the vertebrate neural retina are generated from a pool of multipotent progenitor cells. Recent studies suggest a model of retinal development in which both the progenitor cells and the environment change over time (Cepko, C. L., Austin, C. P., Yang, X., Alexiades, M. and Ezzeddine, D. (1996). Proc. Natl. Acad. Sci. USA 93, 589–595). We have utilized a reaggregate culture system to test this model. A labeled population of progenitors from the embryonic rat retina were cultured with an excess of postnatal retinal cells and then assayed for their cell fate choices. We found that the postnatal environment had at least two signals that affected the embryonic cells' choice of fate; one signal inhibited the production of amacrine cells and a second affected the production of cone cells. No increase in cell types generated postnatally was observed. The source of the inhibitor of the amacrine cell fate appeared to be previously generated amacrine cells, suggesting that amacrine cell number is controlled by feedback inhibition. The progenitor cell lost its ability to be inhibited for production of an amacrine cell as it entered M phase of the cell cycle. We suggest that postmitotic cells influence progenitor cell fate decisions, but that they do so in a manner restricted by the intrinsic biases of progenitor cells.

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