Isthmus progenitor cells contribute to homeostatic cellular turnover and support regeneration following intestinal injury

Ermanno Malagola, Alessandro Vasciaveo, Yosuke Ochiai, Woosook Kim, Biyun Zheng, Luca Zanella, Alexander L.E. Wang, Moritz Middelhoff, Henrik Nienhüser, Lu Deng, Feijing Wu, Quin T. Waterbury, Bryana Belin, Jonathan LaBella, Leah B. Zamechek, Melissa H. Wong, Linheng Li, Chandan Guha, Chia Wei Cheng, Kelley S. YanAndrea Califano, Timothy C. Wang

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The currently accepted intestinal epithelial cell organization model proposes that Lgr5+ crypt-base columnar (CBC) cells represent the sole intestinal stem cell (ISC) compartment. However, previous studies have indicated that Lgr5+ cells are dispensable for intestinal regeneration, leading to two major hypotheses: one favoring the presence of a quiescent reserve ISC and the other calling for differentiated cell plasticity. To investigate these possibilities, we studied crypt epithelial cells in an unbiased fashion via high-resolution single-cell profiling. These studies, combined with in vivo lineage tracing, show that Lgr5 is not a specific ISC marker and that stemness potential exists beyond the crypt base and resides in the isthmus region, where undifferentiated cells participate in intestinal homeostasis and regeneration following irradiation (IR) injury. Our results provide an alternative model of intestinal epithelial cell organization, suggesting that stemness potential is not restricted to CBC cells, and neither de-differentiation nor reserve ISC are drivers of intestinal regeneration.

Original languageEnglish (US)
Pages (from-to)3056-3071.e17
JournalCell
Volume187
Issue number12
DOIs
StatePublished - Jun 6 2024

Keywords

  • adult stem cells
  • cell potency
  • epithelial stem cells
  • intestinal stem cells
  • intestine
  • plasticity
  • regeneration
  • regulatory network analysis
  • single cell
  • stemness signature

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

Fingerprint

Dive into the research topics of 'Isthmus progenitor cells contribute to homeostatic cellular turnover and support regeneration following intestinal injury'. Together they form a unique fingerprint.

Cite this