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Related Concept Videos

Somatic to iPS Cell Reprogramming01:29

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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...
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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...
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Accessory Structures of the Skin: Sweat Glands01:20

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Sweat glands or sudoriferous glands are one of the important accessory structures of the skin. They are small, coiled tubular structures located in the dermis, the middle layer of the skin. Sweat glands are responsible for producing and secreting sweat, a watery fluid that helps regulate body temperature and excrete waste products.
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Transdifferentiation, also known as lineage reprogramming, was first discovered by Selman and Kafatos in 1974 in silkmoths. They observed that the moths’ cuticle-producing cells transformed into salt-producing cells. Many such cases of natural transdifferentiation occur in organisms. In humans, pancreatic alpha cells can become beta cells. In newts, the loss of the eye’s lens causes the pigmented epithelial cells to transdifferentiate into the lens cells.
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Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
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Small molecules facilitate single factor-mediated sweat gland cell reprogramming.

Shuai-Fei Ji1,2, Lai-Xian Zhou1,2, Zhi-Feng Sun3

  • 1Research Center for Tissue Repair and Regeneration Affiliated To Medical Innovation Research Department and 4th Medical Center, PLA General Hospital and PLA Medical College; PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, 28 Fu Xing Road, Beijing, 100853, China.

Military Medical Research
|March 30, 2022
PubMed
Summary
This summary is machine-generated.

This study presents a novel strategy to reprogram human dermal fibroblasts into sweat gland-like cells (iSGCs) using EDA and chemical cocktails. These iSGCs show functional characteristics and potential for in vivo skin regeneration.

Keywords:
Direct reprogrammingHuman dermal fibroblastsRegenerationSweat gland

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Area of Science:

  • Regenerative Medicine
  • Dermatology
  • Cell Biology

Background:

  • Large skin defects can cause irreversible damage to sweat glands (SG), impairing skin function.
  • Developing methods for functional skin repair and regeneration is crucial.
  • Current strategies lack efficient ways to restore damaged SG.

Purpose of the Study:

  • To develop a stepwise reprogramming strategy to convert fibroblasts into SG lineages.
  • To generate functional induced SG-like cells (iSGCs) for skin regeneration.
  • To evaluate the potential of iSGCs for in situ skin repair with SG restoration.

Main Methods:

  • Fibroblast reprogramming using EDA overexpression in SG culture medium (SGM).
  • Treatment with chemical cocktails to accelerate SG fate.
  • Assessment of SG markers (CK5, CK10, CK18, CEA, AQP5) via qPCR, immunofluorescence, and flow cytometry.
  • Functional evaluation using calcium activity analysis and in vivo mouse xenograft models (sweat tests, histology).

Main Results:

  • EDA successfully drove fibroblast conversion into iSGCs, with increased SG marker expression.
  • Chemical cocktails significantly enhanced SG marker expression (CK5, CK18, CK10, AQP5) and functional markers.
  • iSGCs exhibited acetylcholine-induced calcium activity comparable to primary SG cells.
  • In vivo studies showed regenerated SG structures and positive sweat tests in iSGC-treated mice.

Conclusions:

  • A novel SG reprogramming strategy using EDA, SGM, and small molecules effectively generates functional iSGCs from fibroblasts.
  • The generated iSGCs possess functional characteristics and demonstrate potential for in vivo skin regeneration.
  • This approach holds significant implications for future skin regeneration therapies focused on restoring sweat gland function.