The Sox2: <scp>GFP</scp>+/− knock‐in mouse model does not faithfully recapitulate Sox2 expression in skin

Salz, Lucia; Driskell, Ryan R.

doi:10.1111/exd.13396

Cited by 6 publications

(4 citation statements)

References 11 publications

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“…Secondly, we find abrupt changes in 3'UTR to CDS ratios in closely apposed but morphologically distinct tissues, such as Sox2 and Myc in the whisker dermal papillae and a number of genes in Ki67+ vs Ki67-cells in the hair follicle. Sox2 is critical in DP development [26,41] and shows equal 3'UTR to CDS in DP cells, whereas Myc, known for its role in proliferation, shows high 3'UTR. Interestingly, DP cells serve as a reservoir of stem cells (IPSC cells derive from the DP [42][43][44]; the high Myc 3'UTRlow CDS in these cells may allow them to maintain a non-proliferative, quiescent stem cell state.…”

Section: Stem Cell Biologymentioning

confidence: 99%

Distinct expression of select and transcriptome-wide isolated 3’UTRs suggests critical roles in development and transition states

Yang

Gozali

et al. 2021

PLoS ONE

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Mature mRNA molecules are expected to be comprised of a 5’UTR, a 3’UTR and a coding region (CDS). Unexpectedly, however, there have been multiple recent reports of widespread differential expression of mRNA 3’UTRs and their cognate coding regions (CDS), reflecting the expression of isolated 3’UTRs (i3’UTRs); these i3’UTRs can be highly expressed, often in reciprocal patterns to their cognate CDS. As with other long non-coding (lncRNAs), isolated 3’UTRs are likely to play an important role in gene regulation, but little is known about the contexts in which they are deployed. To illuminate the functions of i3’UTRs, here we carry out in vitro, in vivo and in silico analyses of differential 3’UTR/CDS mRNA ratio usage across tissues, development and cell state changes both for a select list of developmentally important genes as well as by unbiased transcriptome-wide analyses. Across two developmental paradigms we find a distinct switch from high i3’UTR expression for stem cell related genes in proliferating cells to high CDS for these genes in newly differentiated cells. Unbiased transcriptome analysis across multiple gene sets shows that regardless of tissue, genes with high 3’UTR to CDS ratios belong predominantly to gene ontology categories related to cell-type specific functions. In contrast, the gene ontology categories of genes with low 3’UTR to CDS ratios are similar across tissues and relate to common cellular functions. We further show that, at least for some genes, traditional transcriptional start site genomic elements correspond to identified RNAseq 3’UTR peak regions, suggesting that some i3’UTRs may be generated by de novo transcription. Our results provide critical information from which detailed hypotheses for individual i3’UTRs can be tested, with a common theme that i3’UTRs appear poised to regulate cell-specific gene expression and state.

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Section: Stem Cell Biologymentioning

confidence: 99%

Distinct expression of select and transcriptome-wide isolated 3’UTRs suggests critical roles in development and transition states

Yang

Gozali

et al. 2021

PLoS ONE

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“…The skin wound specimens were fixed in 4% PFA for 12 hours at 4 o C and then prepared for histological processing according to [31]. Briefly, tissue samples were incubated in 30% sucrose for 24 hours, embedded in OCT, snap-frozen and cryosectioned (50-μm-thick sections).…”

Section: Methodsmentioning

confidence: 99%

Investigating the potential of the secretome of mesenchymal stem cells derived from sickle cell disease patients

et al. 2019

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Sickle cell disease (SCD) is a monogenic red cell disorder associated with multiple vascular complications, microvessel injury and wound-healing deficiency. Although stem cell transplantation with bone marrow-derived mesenchymal stem cells (BMSC) can promote wound healing and tissue repair in SCD patients, therapeutic efficacy is largely dependent on the paracrine activity of the implanted BM stromal cells. Since in vitro expansion and culture conditions are known to modulate the innate characteristics of BMSCs, the present study investigated the effects of normoxic and hypoxic cell-culture preconditioning on the BMSC secretome, in addition to the expression of paracrine molecules that induce angiogenesis and skin regeneration. BMSCs derived from SCD patients were submitted to culturing under normoxic (norCM) and hypoxic (hypoCM) conditions. We found that hypoxically conditioned cells presented increased expression and secretion of several well-characterized trophic growth factors (VEGF, IL8, MCP-1, ANG) directly linked to angiogenesis and tissue repair. The hypoCM secretome presented stronger angiogenic potential than norCM, both in vitro and in vivo, as evidenced by HUVEC proliferation, survival, migration, sprouting formation and in vivo angiogenesis. After local application in a murine wound-healing model, HypoCM showed significantly improved wound closure, as well as enhanced neovascularization in comparison to untreated controls. In sum, the secretome of hypoxia-preconditioned BMSC has increased expression of trophic factors involved in angiogenesis and skin regeneration. Considering that these preconditioned media are easily obtainable, this strategy represents an alternative to stem cell transplantation and could form the basis of novel therapies for vascular regeneration and wound healing in individuals with sickle cell disease.

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“…While it was shown that the GFP+tdT+ population was well enriched in signature DP markers, the tdT+ single population could be attributed to the third-wave Zigzag hairs or DS cells, which are GFPÀ, and the small percentage of GFP+ single population may be the small population in the dermis that expresses Sox2, for instance the Schwann cells (Roberts et al, 2017;Torres-Mejı ´a et al, 2020). Also, even though Sox2 GFP knockin expression has been used by several groups to identify DP cells during morphogenesis and hair cycle, a recent publication has pointed out that these reporter mice do not faithfully report Sox2 endogenous protein levels in the skin, as they have an aberrant expression in the infundibulum and in the DP of HFs (Salz and Driskell, 2017).…”

Section: Limitations Of the Studymentioning

confidence: 99%

Sox2 in the dermal papilla regulates hair follicle pigmentation

Ng¹,

Lim²,

Tan³

et al. 2022

Cell Reports

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The Sox2: GFP+/− knock‐in mouse model does not faithfully recapitulate Sox2 expression in skin

Cited by 6 publications

References 11 publications

Distinct expression of select and transcriptome-wide isolated 3’UTRs suggests critical roles in development and transition states

Distinct expression of select and transcriptome-wide isolated 3’UTRs suggests critical roles in development and transition states

Investigating the potential of the secretome of mesenchymal stem cells derived from sickle cell disease patients

Sox2 in the dermal papilla regulates hair follicle pigmentation

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