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Tracking the cell hierarchy in the human intestine using biochemical signatures derived by mid-infrared microspectroscopy.

Research output: Contribution to journalJournal article

  • Michael John Walsh
  • Azzedine Hammiche
  • Tariq G. Fellous
  • James M. Nicholson
  • Marine Cotte
  • Jean Susini
  • Nigel J. Fullwood
  • Pierre L. Martin-Hirsch
  • Malcolm R. Alison
  • Frank L. Martin
<mark>Journal publication date</mark>07/2009
<mark>Journal</mark>Stem Cell Research
Issue number1
Number of pages13
Pages (from-to)15-27
<mark>Original language</mark>English


Markers of gastrointestinal (GI) stem cells remain elusive. We employed synchrotron Fourier-transform infrared (FTIR) microspectroscopy to derive mid-infrared (IR) spectra along the length of human GI crypts. Tissue sections (10-μm thick) were floated onto BaF2 windows and image maps were acquired of small intestine and large bowel crypts in transmission mode with an aperture of ≤ 10 μm × 10 μm. Counting upwards in a step-size (≤ 10 μm) fashion from the crypt base, IR spectra were extracted from the image maps and each spectrum corresponding to a particular location was identified. Spectra were analyzed using principal component analysis plus linear discriminant analysis. Compared to putative crypt base columnar/Paneth cells, those assigned as label-retaining cells were chemically more similar to putative large bowel stem cells and, the small intestine transit-amplifying cells were closest to large bowel transit-amplifying cells; interestingly, the base of small intestine crypts was the most chemically-distinct. This study suggests that in the complex cell lineage of human GI crypts, chemical similarities as revealed by FTIR microspectroscopy between regions putatively assigned as stem cell, transit-amplifying and terminally-differentiated facilitates identification of cell function.