# Singh 2004: identification of human brain tumour initiating cells

Source: https://onco.cc/key-papers/paper-singh-brain-tumour-initiating-cells-nature-2004/  
OnCo record `paper-singh-brain-tumour-initiating-cells-nature-2004` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The first proof that human brain tumours are driven by a small population of stem-like cells: a hundred cells carrying the CD133 marker could regrow a patient's tumour in a mouse brain while a hundred thousand cells without it could not.

## Summary

Singh, Dirks and colleagues at the Hospital for Sick Children in Toronto isolated CD133-positive cells from human medulloblastomas and glioblastomas and transplanted them into the brains of immunodeficient mice. As few as 100 CD133-positive cells produced tumours that reproduced the histology of the patient's original cancer and could be serially transplanted, whereas up to 100,000 CD133-negative cells did not form tumours. The paper established the brain tumour initiating cell and made CD133 the working marker for glioma stem cells.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: Nature
- Year: 2004
- DOI: 10.1038/nature03128
- Authors: Singh SK, Hawkins C, Clarke ID, et al.
- Findings: CD133-positive cells from human medulloblastoma and glioblastoma initiated tumours in mouse brains from as few as 100 cells.; CD133-negative cells did not form tumours even at 100,000 cells.; Xenografts reproduced the original tumour's phenotype and could be passaged serially.
- What it means: This paper extended the cancer stem cell model to brain tumours and set up the later finding that these cells resist radiotherapy. It is the basis for treatment strategies aimed at the cells that regrow glioblastoma after surgery and chemoradiation.
- Caveats: CD133-negative cells were later shown to initiate tumours in some gliomas, so the marker is imperfect.; Transplantation assays in mice may select for cells that survive the assay.

## Sources

- Full text (DOI): https://doi.org/10.1038/nature03128

## Connected records

- key papers: [Bao 2006: glioma stem cells resist radiotherapy by activating the DNA damage response](https://onco.cc/key-papers/paper-bao-glioma-stem-cells-radioresistance-nature-2006/), [Reya 2001: stem cells, cancer and cancer stem cells](https://onco.cc/key-papers/paper-reya-cancer-stem-cells-nature-2001/)
- cancers: [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/), [Medulloblastoma](https://onco.cc/cancers/medulloblastoma/)
- institutions: [The Hospital for Sick Children (SickKids)](https://onco.cc/institutions/sickkids/)
- terms: [Cancer stem cell theory and phenotypic plasticity](https://onco.cc/terms/cancer-stem-cell-theory/), [Stem cell](https://onco.cc/terms/stem-cell/)
- pathways: [Cancer stem cells & phenotypic plasticity](https://onco.cc/pathways/cancer-stem-cells-plasticity/)

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