Dataset Information

A new Elf5Cre ERT 2- GFP BAC transgenic mouse model for tracing Elf5 cell lineages in adult tissues.

ABSTRACT: Elf5 is a transcription factor known to regulate critical developmental processes and has been shown to act as a tumour suppressor in multiple cancers. Elf5 knockout mice are embryonically lethal, limiting in vivo studies pertaining to its function. Moreover, haploinsufficiency of Elf5 limits the use of current mouse models to investigate adult tissue distribution of Elf5. Here, we successfully generated Elf5Cre ERT 2- GFP bacterial artificial chromosome (BAC) transgenic mice and show that Elf5+ cells are present in several adult tissues, where its expression was previously not known. Our study demonstrates the unique distribution of Elf5+ cells in multiple adult organs, which will facilitate future studies investigating the function of Elf5 in these tissues during homeostasis, repair and cancer.

SUBMITTER: Singh S

PROVIDER: S-EPMC6538489 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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A new Elf5CreERT2-GFP BAC transgenic mouse model for tracing Elf5 cell lineages in adult tissues.

Singh Snahlata S Elenio Emily E Leu Nicolae A NA Romano Rose-Anne RA Vaughan Andrew E AE DeRiso Jennifer J Surendran Kameswaran K Chakrabarti Rumela R

FEBS letters 20190501 10

Elf5 is a transcription factor known to regulate critical developmental processes and has been shown to act as a tumour suppressor in multiple cancers. Elf5 knockout mice are embryonically lethal, limiting in vivo studies pertaining to its function. Moreover, haploinsufficiency of Elf5 limits the use of current mouse models to investigate adult tissue distribution of Elf5. Here, we successfully generated Elf5CreERT2-GFP bacterial artificial chromosome ...[more]

PMID: 31002388

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Project description:BackgroundMyometrium, the muscular wall of the uterus, is an active organ markedly remodeled during a woman's reproductive life, especially during pregnancy. Different studies using the 5-bromo-2'-deoxyuridine and side population methods in murine and human myometrium have suggested the presence of somatic stem cells in this tissue because of its remarkable regenerative capacity. Recently, our group has developed a surface-marker (Stro1/CD44)-specific approach to isolate and characterize myometrial somatic stem cells (SSCs) from humans and rats.ObjectiveIn this study, we aimed to identify and localize the putative myometrial stem cell population in the murine uterus by using the specific surface markers, Nanog/CD44.MethodsUteri from OCT4-GFP transgenic mice at different early-life time points were analyzed via single and double immunohistochemistry to co-localize myometrial stem cell marker CD44 with other general stemmness markers, e.g., Nanog and Oct-4. Finally, we correlated the frequency of myometrial stem cells in vivo with the expression of sex steroid hormone receptors, estrogen receptor α (ERα), and progesterone receptors A and B (PR A&B).ResultsNanog+/CD44+ stem cells were present in murine myometrium. Both stem cell markers were shown to co-localize with Oct-4 expression. Time-course experiments demonstrated that their percentages were significantly lower at the pre-sexual age of 1 week than at the sexually mature ages of 3 to 24 weeks. Importantly, both ERα and PR A&B were abundantly expressed in the myometrium at ages 1, 3 and 4 weeks.ConclusionsWe demonstrated that murine CD44+ myometrial cells have features of somatic stem cells with the expression of typical undifferentiated markers. Furthermore, our results suggest that myometrial stem cells are sex steroid hormone dependent, likely via paracrine pathway, and increase in numbers with reproductive maturity and rise in serum estrogen and progesterone levels around 3 weeks of age in mice. The abundance and early onset expression of ER/PR emphasize the vulnerability of neonatal myometrium to environmental endocrine disruptors which can potentially lead to permanent reprograming and adult onset of myometrial disorders such as uterine fibroids.

Dataset Information

A new Elf5Cre ERT 2- GFP BAC transgenic mouse model for tracing Elf5 cell lineages in adult tissues.

Publications

A new Elf5<sup>Cre</sup><sup>ERT</sup><sup>2-</sup><sup>GFP</sup> BAC transgenic mouse model for tracing Elf5 cell lineages in adult tissues.

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