A new Elf5^{CreERT2‐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 Elf5CreERT2‐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.

554 MicroRNA-148a controls epidermal and hair follicle stem/progenitor cells by modulating the activities of Rock1 and Elf5

“…During cellular differentiation, miR-148a has been shown to regulate skeletal muscle cell differentiation (Yin et al, 2020) and monocyte differentiation into macrophages (Huang et al, 2017). Of interest, inhibition of ROCK1 has been shown to result in the failure of human KCs to terminally differentiate (Chapman et al, 2014;McMullan et al, 2003), which is consistent with our data on PMEKs (Figure 4d-g), whereas ELF5 is essential in the control of mammary cell proliferation and differentiation processes (Zhou et al, 2005) and is expressed in differentiating KCs, inner root sheath, and outer root sheath layers of the HF (Choi et al, 2008;Singh et al, 2019). Our data suggest that in the epidermis, miR-148a may function, in part, by restricting the proliferative potential of stem/progenitors as they transitioned from basal to suprabasal layers through the regulation of Rock1 and Elf5 expression.…”

“…In addition, studies have suggested that ROCK1 signaling inhibition elevates stem/progenitor cell functions, in vitro (Centonze et al, 2022). Furthermore, ROCK1 has been shown to promote embryonic SC colony formation and maintenance of neural progenitor cells (Chang et al, 2010), whereas Elf5 is expressed in differentiated epidermal and oral mouse KCs as well as in the inner root sheath and outer root sheath of HFs (Choi et al, 2008;Oakes et al, 2008;Parikh et al, 2008;Singh et al, 2019;Tummala and Sinha, 2006). However, Elf5's functional role in these cell populations has not been determined.…”