| Autor: |
Breanna J. Sheahan, Ally N. Freeman, Theresa M. Keeley, Linda C. Samuelson, Jatin Roper, Stephanie Hasapis, Chang-Lung Lee, Christopher M. Dekaney |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Cellular and Molecular Gastroenterology and Hepatology, Vol 12, Iss 1, Pp 119-140 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2352-345X |
| DOI: |
10.1016/j.jcmgh.2021.01.015 |
| Popis: |
Background & Aims: aISCs (aISCs) are sensitive to acute insults including chemotherapy and irradiation. Regeneration after aISC depletion has primarily been explored in irradiation (IR). However, the cellular origin of epithelial regeneration after doxorubicin (DXR), a common chemotherapeutic, is poorly understood. Methods: We monitored DXR’s effect on aISCs by enumerating Lgr5-eGFP+ and Olfm4+ crypts, cleaved caspase-3 (CASP3+) immunofluorescence, and time-lapse organoid imaging. Lineage tracing from previously identified regenerative cell populations (Bmi1+, Hopx+, Dll1+, and Defa6+) was performed with DXR damage. Lineage tracing from aISCs was compared with lineage tracing from early progeny cells (transit-amplifying cells arising from aISCs 1 day predamage) in the context of DXR and IR. We compared stem cell and DNA damage response (DDR) transcripts in isolated aISCs and early progeny cells 6 and 24 hours after DXR. Results: Epithelial regeneration after DXR primarily arose from early progeny cells generated by aISCs. Early progeny cells upregulated stem cell gene expression and lacked apoptosis induction (6 hours DXR: 2.5% of CASP3+ cells, p |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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