Origin of the brush cell lineage in the mouse intestinal epithelium

Matthew Bjerknes, Cyrus Khandanpour, Tarik Möröy, Tomoyuki Fujiyama, Mikio Hoshino, Tiemo J. Klisch, Qian Ding, Lin Gan, Jiafang Wang, Martín G. Martín, Hazel Cheng

Research output: Contribution to journalArticle

Abstract

Mix progenitors are short-lived multipotential cells formed as intestinal epithelial stem cells initiate a differentiation program. Clone dynamics indicates that various epithelial cell lineages arise from Mix via a sequence of progressively restricted progenitor states. Lateral inhibitory Notch signaling between the daughters of Mix (DOM) is thought to break their initial symmetry, thereby determining whether a DOM invokes a columnar (absorptive) or granulocytic (secretory) cell lineage program. This is supported by the absence of granulocytes following enforced Notch signaling or Atoh1 deletion. Conversely, granulocytes increase in frequency following inhibition of Notch signaling or Hes1 deletion. Thus reciprocal repression between Hes1 and Atoh1 is thought to implement a Notch signaling-driven cell-fate-determining binary switch in DOM. The brush (tuft) cells, a poorly understood chemosensory cell type, are not incorporated into this model. We report that brush cell numbers increase dramatically following conditional Atoh1-deletion, demonstrating that brush cell production, determination, differentiation and survival are Atoh1-independent. We also report that brush cells are derived from Gfi1b-expressing progenitors. These and related results suggest a model in which initially equivalent DOM progenitors have three metastable states defined by the transcription factors Hes1, Atoh1, and Gfi1b. Lateral inhibitory Notch signaling normally ensures that Hes1 dominates in one of the two DOMs, invoking a columnar lineage program, while either Atoh1 or Gfi1b dominates in the other DOM, invoking a granulocytic or brush cell lineage program, respectively, and thus implementing a cell fate-determining ternary switch.

Original languageEnglish (US)
Pages (from-to)194-218
Number of pages25
JournalDevelopmental Biology
Volume362
Issue number2
DOIs
StatePublished - Feb 15 2012
Externally publishedYes

Fingerprint

Cell Lineage
Intestinal Mucosa
Granulocytes
2,5-Dimethoxy-4-Methylamphetamine
Epithelial Cells
Transcription Factors
Stem Cells
Clone Cells
Cell Count

Keywords

  • Atoh1
  • Brush cell
  • Gfi1b
  • Hes1
  • Intestinal stem cell
  • Notch signaling
  • Tuft cell

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Bjerknes, M., Khandanpour, C., Möröy, T., Fujiyama, T., Hoshino, M., Klisch, T. J., ... Cheng, H. (2012). Origin of the brush cell lineage in the mouse intestinal epithelium. Developmental Biology, 362(2), 194-218. https://doi.org/10.1016/j.ydbio.2011.12.009

Origin of the brush cell lineage in the mouse intestinal epithelium. / Bjerknes, Matthew; Khandanpour, Cyrus; Möröy, Tarik; Fujiyama, Tomoyuki; Hoshino, Mikio; Klisch, Tiemo J.; Ding, Qian; Gan, Lin; Wang, Jiafang; Martín, Martín G.; Cheng, Hazel.

In: Developmental Biology, Vol. 362, No. 2, 15.02.2012, p. 194-218.

Research output: Contribution to journalArticle

Bjerknes, M, Khandanpour, C, Möröy, T, Fujiyama, T, Hoshino, M, Klisch, TJ, Ding, Q, Gan, L, Wang, J, Martín, MG & Cheng, H 2012, 'Origin of the brush cell lineage in the mouse intestinal epithelium', Developmental Biology, vol. 362, no. 2, pp. 194-218. https://doi.org/10.1016/j.ydbio.2011.12.009
Bjerknes M, Khandanpour C, Möröy T, Fujiyama T, Hoshino M, Klisch TJ et al. Origin of the brush cell lineage in the mouse intestinal epithelium. Developmental Biology. 2012 Feb 15;362(2):194-218. https://doi.org/10.1016/j.ydbio.2011.12.009
Bjerknes, Matthew ; Khandanpour, Cyrus ; Möröy, Tarik ; Fujiyama, Tomoyuki ; Hoshino, Mikio ; Klisch, Tiemo J. ; Ding, Qian ; Gan, Lin ; Wang, Jiafang ; Martín, Martín G. ; Cheng, Hazel. / Origin of the brush cell lineage in the mouse intestinal epithelium. In: Developmental Biology. 2012 ; Vol. 362, No. 2. pp. 194-218.
@article{61c1cf43855c4ead8af0a79abeb5fe80,
title = "Origin of the brush cell lineage in the mouse intestinal epithelium",
abstract = "Mix progenitors are short-lived multipotential cells formed as intestinal epithelial stem cells initiate a differentiation program. Clone dynamics indicates that various epithelial cell lineages arise from Mix via a sequence of progressively restricted progenitor states. Lateral inhibitory Notch signaling between the daughters of Mix (DOM) is thought to break their initial symmetry, thereby determining whether a DOM invokes a columnar (absorptive) or granulocytic (secretory) cell lineage program. This is supported by the absence of granulocytes following enforced Notch signaling or Atoh1 deletion. Conversely, granulocytes increase in frequency following inhibition of Notch signaling or Hes1 deletion. Thus reciprocal repression between Hes1 and Atoh1 is thought to implement a Notch signaling-driven cell-fate-determining binary switch in DOM. The brush (tuft) cells, a poorly understood chemosensory cell type, are not incorporated into this model. We report that brush cell numbers increase dramatically following conditional Atoh1-deletion, demonstrating that brush cell production, determination, differentiation and survival are Atoh1-independent. We also report that brush cells are derived from Gfi1b-expressing progenitors. These and related results suggest a model in which initially equivalent DOM progenitors have three metastable states defined by the transcription factors Hes1, Atoh1, and Gfi1b. Lateral inhibitory Notch signaling normally ensures that Hes1 dominates in one of the two DOMs, invoking a columnar lineage program, while either Atoh1 or Gfi1b dominates in the other DOM, invoking a granulocytic or brush cell lineage program, respectively, and thus implementing a cell fate-determining ternary switch.",
keywords = "Atoh1, Brush cell, Gfi1b, Hes1, Intestinal stem cell, Notch signaling, Tuft cell",
author = "Matthew Bjerknes and Cyrus Khandanpour and Tarik M{\"o}r{\"o}y and Tomoyuki Fujiyama and Mikio Hoshino and Klisch, {Tiemo J.} and Qian Ding and Lin Gan and Jiafang Wang and Mart{\'i}n, {Mart{\'i}n G.} and Hazel Cheng",
year = "2012",
month = "2",
day = "15",
doi = "10.1016/j.ydbio.2011.12.009",
language = "English (US)",
volume = "362",
pages = "194--218",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Origin of the brush cell lineage in the mouse intestinal epithelium

AU - Bjerknes, Matthew

AU - Khandanpour, Cyrus

AU - Möröy, Tarik

AU - Fujiyama, Tomoyuki

AU - Hoshino, Mikio

AU - Klisch, Tiemo J.

AU - Ding, Qian

AU - Gan, Lin

AU - Wang, Jiafang

AU - Martín, Martín G.

AU - Cheng, Hazel

PY - 2012/2/15

Y1 - 2012/2/15

N2 - Mix progenitors are short-lived multipotential cells formed as intestinal epithelial stem cells initiate a differentiation program. Clone dynamics indicates that various epithelial cell lineages arise from Mix via a sequence of progressively restricted progenitor states. Lateral inhibitory Notch signaling between the daughters of Mix (DOM) is thought to break their initial symmetry, thereby determining whether a DOM invokes a columnar (absorptive) or granulocytic (secretory) cell lineage program. This is supported by the absence of granulocytes following enforced Notch signaling or Atoh1 deletion. Conversely, granulocytes increase in frequency following inhibition of Notch signaling or Hes1 deletion. Thus reciprocal repression between Hes1 and Atoh1 is thought to implement a Notch signaling-driven cell-fate-determining binary switch in DOM. The brush (tuft) cells, a poorly understood chemosensory cell type, are not incorporated into this model. We report that brush cell numbers increase dramatically following conditional Atoh1-deletion, demonstrating that brush cell production, determination, differentiation and survival are Atoh1-independent. We also report that brush cells are derived from Gfi1b-expressing progenitors. These and related results suggest a model in which initially equivalent DOM progenitors have three metastable states defined by the transcription factors Hes1, Atoh1, and Gfi1b. Lateral inhibitory Notch signaling normally ensures that Hes1 dominates in one of the two DOMs, invoking a columnar lineage program, while either Atoh1 or Gfi1b dominates in the other DOM, invoking a granulocytic or brush cell lineage program, respectively, and thus implementing a cell fate-determining ternary switch.

AB - Mix progenitors are short-lived multipotential cells formed as intestinal epithelial stem cells initiate a differentiation program. Clone dynamics indicates that various epithelial cell lineages arise from Mix via a sequence of progressively restricted progenitor states. Lateral inhibitory Notch signaling between the daughters of Mix (DOM) is thought to break their initial symmetry, thereby determining whether a DOM invokes a columnar (absorptive) or granulocytic (secretory) cell lineage program. This is supported by the absence of granulocytes following enforced Notch signaling or Atoh1 deletion. Conversely, granulocytes increase in frequency following inhibition of Notch signaling or Hes1 deletion. Thus reciprocal repression between Hes1 and Atoh1 is thought to implement a Notch signaling-driven cell-fate-determining binary switch in DOM. The brush (tuft) cells, a poorly understood chemosensory cell type, are not incorporated into this model. We report that brush cell numbers increase dramatically following conditional Atoh1-deletion, demonstrating that brush cell production, determination, differentiation and survival are Atoh1-independent. We also report that brush cells are derived from Gfi1b-expressing progenitors. These and related results suggest a model in which initially equivalent DOM progenitors have three metastable states defined by the transcription factors Hes1, Atoh1, and Gfi1b. Lateral inhibitory Notch signaling normally ensures that Hes1 dominates in one of the two DOMs, invoking a columnar lineage program, while either Atoh1 or Gfi1b dominates in the other DOM, invoking a granulocytic or brush cell lineage program, respectively, and thus implementing a cell fate-determining ternary switch.

KW - Atoh1

KW - Brush cell

KW - Gfi1b

KW - Hes1

KW - Intestinal stem cell

KW - Notch signaling

KW - Tuft cell

UR - http://www.scopus.com/inward/record.url?scp=84856089512&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84856089512&partnerID=8YFLogxK

U2 - 10.1016/j.ydbio.2011.12.009

DO - 10.1016/j.ydbio.2011.12.009

M3 - Article

C2 - 22185794

AN - SCOPUS:84856089512

VL - 362

SP - 194

EP - 218

JO - Developmental Biology

JF - Developmental Biology

SN - 0012-1606

IS - 2

ER -