Dynamic and adaptive cancer stem cell population admixture in colorectal neoplasia
Intestinal homeostasis is underpinned by LGR5+ve crypt-base columnar stem cells (CBCs), but following injury, dedifferentiation results in the emergence of LGR5−ve regenerative stem cell populations (RSCs), characterized by fetal transcriptional profiles. Neoplasia hijacks regenerative signaling, so...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Cell Press
2022
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| _version_ | 1797107453340418048 |
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| author | Gil Vasquez, E Nasreddin, N Valbuena, G Mulholland, E Belnoue Davis, H Eggington, H Schenck, R Wouters, V Wirapati, P Gilroy, K Lannagan, T Flanagan, D Najumudeen, A Omwenga, S McCorrry, A Easton, A Koelzer, V East, J Morton, D Trusolino, L Maughan, T Campbell, A Loughrey, M Dunne, P Tsantoulis, P Huels, D Tejpar, S Sansom, O Leedham, S |
| author_facet | Gil Vasquez, E Nasreddin, N Valbuena, G Mulholland, E Belnoue Davis, H Eggington, H Schenck, R Wouters, V Wirapati, P Gilroy, K Lannagan, T Flanagan, D Najumudeen, A Omwenga, S McCorrry, A Easton, A Koelzer, V East, J Morton, D Trusolino, L Maughan, T Campbell, A Loughrey, M Dunne, P Tsantoulis, P Huels, D Tejpar, S Sansom, O Leedham, S |
| author_sort | Gil Vasquez, E |
| collection | OXFORD |
| description | Intestinal homeostasis is underpinned by LGR5+ve crypt-base columnar stem cells (CBCs), but following injury, dedifferentiation results in the emergence of LGR5−ve regenerative stem cell populations (RSCs), characterized by fetal transcriptional profiles. Neoplasia hijacks regenerative signaling, so we assessed the distribution of CBCs and RSCs in mouse and human intestinal tumors. Using combined molecular-morphological analysis, we demonstrate variable expression of stem cell markers across a range of lesions. The degree of CBC-RSC admixture was associated with both epithelial mutation and microenvironmental signaling disruption and could be mapped across disease molecular subtypes. The CBC-RSC equilibrium was adaptive, with a dynamic response to acute selective pressure, and adaptability was associated with chemoresistance. We propose a fitness landscape model where individual tumors have equilibrated stem cell population distributions along a CBC-RSC phenotypic axis. Cellular plasticity is represented by position shift along this axis and is influenced by cell-intrinsic, extrinsic, and therapeutic selective pressures. |
| first_indexed | 2024-03-07T07:14:49Z |
| format | Journal article |
| id | oxford-uuid:18452046-facb-41f2-a946-96375e95a964 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:14:49Z |
| publishDate | 2022 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:18452046-facb-41f2-a946-96375e95a9642022-08-10T12:03:54ZDynamic and adaptive cancer stem cell population admixture in colorectal neoplasiaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:18452046-facb-41f2-a946-96375e95a964EnglishSymplectic ElementsCell Press2022Gil Vasquez, ENasreddin, NValbuena, GMulholland, EBelnoue Davis, HEggington, HSchenck, RWouters, VWirapati, PGilroy, KLannagan, TFlanagan, DNajumudeen, AOmwenga, SMcCorrry, AEaston, AKoelzer, VEast, JMorton, DTrusolino, LMaughan, TCampbell, ALoughrey, MDunne, PTsantoulis, PHuels, DTejpar, SSansom, OLeedham, SIntestinal homeostasis is underpinned by LGR5+ve crypt-base columnar stem cells (CBCs), but following injury, dedifferentiation results in the emergence of LGR5−ve regenerative stem cell populations (RSCs), characterized by fetal transcriptional profiles. Neoplasia hijacks regenerative signaling, so we assessed the distribution of CBCs and RSCs in mouse and human intestinal tumors. Using combined molecular-morphological analysis, we demonstrate variable expression of stem cell markers across a range of lesions. The degree of CBC-RSC admixture was associated with both epithelial mutation and microenvironmental signaling disruption and could be mapped across disease molecular subtypes. The CBC-RSC equilibrium was adaptive, with a dynamic response to acute selective pressure, and adaptability was associated with chemoresistance. We propose a fitness landscape model where individual tumors have equilibrated stem cell population distributions along a CBC-RSC phenotypic axis. Cellular plasticity is represented by position shift along this axis and is influenced by cell-intrinsic, extrinsic, and therapeutic selective pressures. |
| spellingShingle | Gil Vasquez, E Nasreddin, N Valbuena, G Mulholland, E Belnoue Davis, H Eggington, H Schenck, R Wouters, V Wirapati, P Gilroy, K Lannagan, T Flanagan, D Najumudeen, A Omwenga, S McCorrry, A Easton, A Koelzer, V East, J Morton, D Trusolino, L Maughan, T Campbell, A Loughrey, M Dunne, P Tsantoulis, P Huels, D Tejpar, S Sansom, O Leedham, S Dynamic and adaptive cancer stem cell population admixture in colorectal neoplasia |
| title | Dynamic and adaptive cancer stem cell population admixture in colorectal neoplasia |
| title_full | Dynamic and adaptive cancer stem cell population admixture in colorectal neoplasia |
| title_fullStr | Dynamic and adaptive cancer stem cell population admixture in colorectal neoplasia |
| title_full_unstemmed | Dynamic and adaptive cancer stem cell population admixture in colorectal neoplasia |
| title_short | Dynamic and adaptive cancer stem cell population admixture in colorectal neoplasia |
| title_sort | dynamic and adaptive cancer stem cell population admixture in colorectal neoplasia |
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