Intracellular pH dynamics regulates intestinal stem cell fate

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

Nature Cell Biology ◽

10.1038/s41556-020-00617-2 ◽

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

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Regulation of intestinal stem cell fate specification

Science China Life Sciences ◽

10.1007/s11427-015-4859-7 ◽

2015 ◽

Vol 58 (6) ◽

pp. 570-578 ◽

Cited By ~ 9

Author(s):

Zhen Qi ◽

Ye-Guang Chen

Keyword(s):

Stem Cell ◽

Cell Fate ◽

Intestinal Stem Cell ◽

Cell Fate Specification ◽

Stem Cell Fate ◽

Fate Specification

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Biomimetic three-dimensional microenvironment for controlling stem cell fate

Interface Focus ◽

10.1098/rsfs.2011.0035 ◽

2011 ◽

Vol 1 (5) ◽

pp. 792-803 ◽

Cited By ~ 41

Author(s):

Hu Zhang ◽

Sheng Dai ◽

Jingxiu Bi ◽

Kuo-Kang Liu

Keyword(s):

Stem Cell ◽

Cell Fate ◽

Three Dimensional ◽

Cell Lineage ◽

Cell Interaction ◽

Stem Cell Fate ◽

Cell Microenvironment ◽

Stem Cell Lineage ◽

Matrix Cell ◽

The Individual

Stem cell therapy is an emerging technique which is being translated into treatment of degenerated tissues. However, the success of translation relies on the stem cell lineage commitment in the degenerated regions of interest. This commitment is precisely controlled by the stem cell microenvironment. Engineering a biomimetic three-dimensional microenvironment enables a thorough understanding of the mechanisms of governing stem cell fate. We review the individual microenvironment components, including soluble factors, extracellular matrix, cell–cell interaction and mechanical stimulation. The perspectives in creating the biomimetic microenvironments are discussed with emerging techniques.

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Slit/Robo Signaling Regulates Cell Fate Decisions in the Intestinal Stem Cell Lineage of Drosophila

Cell Reports ◽

10.1016/j.celrep.2014.05.024 ◽

2014 ◽

Vol 7 (6) ◽

pp. 1867-1875 ◽

Cited By ~ 97

Author(s):

Benoît Biteau ◽

Heinrich Jasper

Keyword(s):

Stem Cell ◽

Cell Fate ◽

Cell Lineage ◽

Intestinal Stem Cell ◽

Cell Fate Decisions ◽

Stem Cell Lineage

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Faster, higher, stronger: timely and robust cell fate/identity commitment in stem cell lineages

Open Biology ◽

10.1098/rsob.180243 ◽

2019 ◽

Vol 9 (2) ◽

pp. 180243 ◽

Cited By ~ 2

Author(s):

Kun Liu ◽

Ke Xu ◽

Yan Song

Keyword(s):

Stem Cell ◽

Cell Fate ◽

Transcriptional Control ◽

Cell Lineage ◽

Cell Fate Specification ◽

Developmental Abnormalities ◽

Cell Lineages ◽

Identity Commitment ◽

Regulatory Strategies ◽

Stem Cell Lineage

Precise specification of cell fate or identity within stem cell lineages is critical for ensuring correct stem cell lineage progression and tissue homeostasis. Failure to specify cell fate or identity in a timely and robust manner can result in developmental abnormalities and diseases such as cancer. However, the molecular basis of timely cell fate/identity specification is only beginning to be understood. In this review, we discuss key regulatory strategies employed in cell fate specification and highlight recent results revealing how timely and robust cell fate/identity commitment is achieved through transcriptional control.

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