Deciphering "Immaturity-Stemness" in Human Epidermal Stem Cells at the Levels of Protein-Coding and Non-Coding
Tatiana Vinasco-Sandoval1,2,3, Gilles Lemaître2,4, Pascal Soularue1,2
1Université Paris-Saclay, 91190 Gif-sur-Yvette, France.
International Journal of Molecular Sciences
|March 28, 2024
Summary
Researchers explored molecular regulators of human skin stem cell renewal. Down-regulating KLF4 or MXD4 enhanced stemness, revealing new insights into keratinocyte stem cell regulation and potential therapeutic targets.
Area of Science:
- Dermatology
- Stem Cell Biology
- Molecular Biology
Background:
- The epidermis contains epithelial stem cells crucial for skin renewal and regeneration.
- Human skin stem cell molecular characteristics are not fully understood.
- Keratinocyte stem and precursor cells in human interfollicular epidermis regulate stemness versus differentiation.
Purpose of the Study:
- Investigate regulatory functions of KLF4/TGFB1 and MAD4/MAX/MYC pathways in keratinocyte stemness.
- Identify molecular regulators controlling the balance between stemness and differentiation in human skin stem cells.
- Integrate coding and non-coding genomic elements to understand stemness regulation.
Main Methods:
- Utilized RNA interference to down-modulate KLF4 and MXD4/MAD4.
- Performed RNA-sequencing to assess transcriptional changes.
- Implemented computational approaches to integrate coding genome, long non-coding RNAs (lncRNAs), and micro-RNAs (miRNAs).
Main Results:
- Down-modulation of KLF4 or MXD4/MAD4 promoted enhanced stemness in keratinocyte stem cells.
- Significant transcriptional changes were observed following gene down-modulation.
- Identified putative regulons linking coding and non-coding transcripts, including lncRNAs and miRNAs.
Conclusions:
- KLF4 and MXD4/MAD4 play key roles in controlling keratinocyte stemness.
- A computational approach integrating multi-omics data provides a comprehensive view of stemness regulation.
- Identified novel candidate effectors for stemness regulation in human skin stem cells, paving the way for functional validation.
Related Concept Videos
01:12Renewal of Skin Epidermal Stem Cells
2.5K
The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular...
2.5K
00:57Embryonic Stem Cells
3.5K
Embryonic stem (ES) cells were first discovered in mice in 1981 by Martin Evans. In 1998, James Thomson identified a method to isolate embryonic stem cells from humans. Human embryonic stem cells (hESCs) are obtained from 3-5 day old embryos that remain unused after an in vitro fertilization procedure.
ES cells are grown in a culture medium where they can divide indefinitely, creating ES cell lines. Under certain conditions, ES cells can differentiate, either spontaneously into a variety of...
ES cells are grown in a culture medium where they can divide indefinitely, creating ES cell lines. Under certain conditions, ES cells can differentiate, either spontaneously into a variety of...
3.5K
01:24Methods of Nuclear Reprogramming
1.8K
Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
1.8K
01:29Somatic to iPS Cell Reprogramming
2.2K
Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
2.2K
01:19Clinical Applications of Epidermal Stem Cells
2.7K
Epidermal stem cells (EpiSCs) are mainly located at the basal layer of the epidermis. These cells repair minor injuries of the skin and replace dead skin cells. However, EpiSCs’ cannot heal severe wounds such as major burns or those from diabetes or hereditary disorders. In such cases, culturing the epidermal stem cells from the patient is possible and has yielded successful treatment options, such as laboratory-grown skin grafts. These grafts are synthesized using a patient’s own...
2.7K
01:14Maintenance of the ES Cell State
2.2K
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
2.2K