scholarly journals Shavenbaby protein isoforms orchestrate the self-renewalversusdifferentiation ofDrosophilaintestinal stem cells

2019 ◽  
Author(s):  
Sandy Al Hayek ◽  
Ahmad Alsawadi ◽  
Zakaria Kambris ◽  
Jean-Philippe Boquete ◽  
Jérôme Bohère ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lineage ◽  
Adult Stem Cell ◽  
Regulatory Peptides ◽  
Protein Isoforms ◽  
Cell Renewal ◽  
Stem Cell Renewal ◽  
Polished Rice ◽  
Stem Cell Lineage ◽  
Underlying Mechanisms

SUMMARYSignaling pathways are key regulators of adult stem cell homeostasis and underlying mechanisms are often deregulated in cancers. Recent studies of epithelial tumors have involved OvoL/Svb transcription factors, which produce isoforms with antagonistic activities. Here we show that Svb, the unique OvoL factor inDrosophila, directly integrates multiple signaling inputs to coordinate the behavior of adult intestinal stem cell lineage. Under steady state, Svb mediates Wnt and EGFR signaling to ensure stem cell renewal and progenitor survival. This requires the post-translational processing of Svb into a transcriptional activator by Polished rice (Pri) regulatory peptides, under the regulation of ecdysone signaling. In response to PDM1, Svb expression is specifically maintained in enterocytes where it acts as a transcriptional repressor sufficient to override mitogenic signals and impose differentiation. Altogether, these results demonstrate that the OvoL/Svb transcriptional switch controls the balance between stem cell survival, self-renewal and differentiation.

scholarly journals Adult stem cell lineage tracing and deep tissue imaging

BMB Reports ◽  
2015 ◽  
Vol 48 (12) ◽  
pp. 655-667 ◽  
Author(s):  
Juergen Fink ◽  
Amanda Andersson-Rolf ◽  
Bon-Kyoung Koo
Keyword(s):  
Stem Cell ◽  
Cell Lineage ◽  
Adult Stem Cell ◽  
Lineage Tracing ◽  
Tissue Imaging ◽  
Deep Tissue ◽  
Stem Cell Lineage ◽  
Deep Tissue Imaging

scholarly journals Accumulation of a differentiation regulator specifies transit amplifying division number in an adult stem cell lineage

2009 ◽  
Vol 106 (52) ◽  
pp. 22311-22316 ◽  
Author(s):  
Megan L. Insco ◽  
Arlene Leon ◽  
Cheuk Ho Tam ◽  
Dennis M. McKearin ◽  
Margaret T. Fuller
Keyword(s):  
Stem Cell ◽  
Cell Lineage ◽  
Adult Stem Cell ◽  
Stem Cell Lineage ◽  
Division Number

scholarly journals A Self-Limiting Switch Based on Translational Control Regulates the Transition from Proliferation to Differentiation in an Adult Stem Cell Lineage

2012 ◽  
Vol 11 (5) ◽  
pp. 689-700 ◽  
Author(s):  
Megan L. Insco ◽  
Alexis S. Bailey ◽  
Jongmin Kim ◽  
Gonzalo H. Olivares ◽  
Orly L. Wapinski ◽  
...  
Keyword(s):  
Stem Cell ◽  
Translational Control ◽  
Cell Lineage ◽  
Adult Stem Cell ◽  
Stem Cell Lineage

scholarly journals Fluctuating methylation clocks for cell lineage tracing at high temporal resolution in human tissues

2022 ◽  
Author(s):  
Calum Gabbutt ◽  
Ryan O. Schenck ◽  
Daniel J. Weisenberger ◽  
Christopher Kimberley ◽  
Alison Berner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lineage ◽  
Adult Stem Cell ◽  
Lineage Tracing ◽  
Rapid Expansion ◽  
High Temporal Resolution ◽  
Molecular Clocks ◽  
Cell Renewal ◽  
Cell Dynamics ◽  
Small Intestinal

AbstractMolecular clocks that record cell ancestry mutate too slowly to measure the short-timescale dynamics of cell renewal in adult tissues. Here, we show that fluctuating DNA methylation marks can be used as clocks in cells where ongoing methylation and demethylation cause repeated ‘flip–flops’ between methylated and unmethylated states. We identify endogenous fluctuating CpG (fCpG) sites using standard methylation arrays and develop a mathematical model to quantitatively measure human adult stem cell dynamics from these data. Small intestinal crypts were inferred to contain slightly more stem cells than the colon, with slower stem cell replacement in the small intestine. Germline APC mutation increased the number of replacements per crypt. In blood, we measured rapid expansion of acute leukemia and slower growth of chronic disease. Thus, the patterns of human somatic cell birth and death are measurable with fluctuating methylation clocks (FMCs).

scholarly journals Intracellular pH dynamics regulates intestinal stem cell fate

2021 ◽  
Author(s):  
Diane L. Barber ◽  
Yi Liu ◽  
Efren Reyes ◽  
David Castillo-Azofeifa ◽  
Ophir D Klein ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Intracellular Ph ◽  
Paneth Cell ◽  
Cell Lineage ◽  
Adult Stem Cell ◽  
Intestinal Stem Cell ◽  
Cell Fate Specification ◽  
Stem Cell Fate ◽  
Stem Cell Lineage

Emerging evidence is revealing critical roles of intracellular pH (pHi) in development, but it remains unclear whether pHi regulates stem cell fate specification. We find that pHi dynamics is a key regulator of cell fate in the mouse intestinal stem cell lineage. We identify a pHi gradient along the intestinal crypt axis and find that dissipating this gradient inhibits crypt budding due to loss Paneth cell differentiation. Mechanistically, decreasing pHi biases intestinal stem cell fate toward the absorptive and away from the secretory lineage, by regulating the activity of the lineage transcription factor Atoh1. Our findings reveal a previously unrecognized role for pHi dynamics in the specification of cell fate within an adult stem cell lineage.

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