scholarly journals Non-canonical Wnt/PCP signalling regulates intestinal stem cell lineage priming towards enteroendocrine and Paneth cell fates

2021 ◽  
Vol 23 (1) ◽  
pp. 23-31
Author(s):  
Anika Böttcher ◽  
Maren Büttner ◽  
Sophie Tritschler ◽  
Michael Sterr ◽  
Alexandra Aliluev ◽  
...  
Keyword(s):  
Stem Cell ◽  
Paneth Cell ◽  
Cell Lineage ◽  
Intestinal Stem Cell ◽  
Cell Fates ◽  
Stem Cell Lineage ◽  
Lineage Priming ◽  
Canonical Wnt

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.

scholarly journals Generation and Staining of Intestinal Stem Cell Lineage in Adult Midgut

2012 ◽  
pp. 47-69 ◽  
Author(s):  
Shree Ram Singh ◽  
Manoj K. Mishra ◽  
Madhuri Kango-Singh ◽  
Steven X. Hou
Keyword(s):  
Stem Cell ◽  
Cell Lineage ◽  
Intestinal Stem Cell ◽  
Stem Cell Lineage

scholarly journals Notch-Mediated Suppression of TSC2 Expression Regulates Cell Differentiation in the Drosophila Intestinal Stem Cell Lineage

PLoS Genetics ◽  
2012 ◽  
Vol 8 (11) ◽  
pp. e1003045 ◽  
Author(s):  
Subir Kapuria ◽  
Jason Karpac ◽  
Benoit Biteau ◽  
DaeSung Hwangbo ◽  
Heinrich Jasper
Keyword(s):  
Stem Cell ◽  
Cell Differentiation ◽  
Cell Lineage ◽  
Intestinal Stem Cell ◽  
Stem Cell Lineage

scholarly journals Wnt/PCP-primed intestinal stem cells directly differentiate into enteroendocrine or Paneth cells

2020 ◽  
Author(s):  
Anika Böttcher ◽  
Maren Büttner ◽  
Sophie Tritschler ◽  
Michael Sterr ◽  
Alexandra Aliluev ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Planar Cell Polarity ◽  
Paneth Cell ◽  
Cell Lineage ◽  
Paneth Cells ◽  
Transcriptional Level ◽  
Self Renewal ◽  
Lineage Priming

SUMMARYA detailed understanding of intestinal stem cell (ISC) self-renewal and differentiation is required to better treat chronic intestinal diseases. However, different models of ISC lineage hierarchy1–6 and segregation7–12 are debated. Here we report the identification of Lgr5+ ISCs that express Flattop (Fltp), a Wnt/planar cell polarity (PCP) reporter and effector gene. Lineage labelling revealed that Wnt/PCP-activated Fltp+ ISCs are primed either towards the enteroendocrine or the Paneth cell lineage in vivo. Integration of time-resolved lineage labelling with genome-wide and targeted single-cell gene expression analysis allowed us to delineate the ISC differentiation path into enteroendocrine and Paneth cells at the molecular level. Strikingly, we found that both lineages are directly recruited from ISCs via unipotent transition states, challenging the existence of formerly predicted bi- or multipotent secretory progenitors7–12. Transitory cells that mature into Paneth cells are quiescent and express both stem cell and secretory lineage genes, indicating that these cells are the previously described Lgr5+ labelretaining cells7. Wnt/PCP-activated Lgr5+ ISCs are indistinguishable from Wnt/β-catenin-activated Lgr5+ ISCs based on the expression of stem-cell signature or secretory lineagespecifying genes but possess less self-renewal activity. This suggests that lineage priming and cell-cycle exit is triggered at the post-transcriptional level by polarity cues and a switch from canonical to non-canonical Wnt/PCP signalling. Taken together, we identified the Wnt/PCP pathway as a new niche signal and polarity cue regulating stem cell fate. Active Wnt/PCP signalling represents one of the earliest events in ISC lineage priming towards the Paneth and enteroendocrine cell fate, preceding lateral inhibition and expression of secretory lineagespecifying genes. Thus, our findings provide a better understanding of the niche signals and redefine the mechanisms underlying ISC lineage hierarchy and segregation.

Sign in / Sign up

Export Citation Format

Share Document