Optogenetic manipulation of BMP signaling to drive chondrogenic differentiation of hPSCs DOI Creative Commons
Paul A. Humphreys, Steven Paul Woods, Nicola Bates

и другие.

Cell Reports, Год журнала: 2023, Номер 42(12), С. 113502 - 113502

Опубликована: Ноя. 29, 2023

Optogenetics is a rapidly advancing technology combining photochemical, optical, and synthetic biology to control cellular behavior. Together, sensitive light-responsive optogenetic tools human pluripotent stem cell differentiation models have the potential fine-tune unpick processes by which specification tissue patterning are controlled morphogens. We used an bone morphogenetic protein (BMP) signaling system (optoBMP) drive chondrogenic of embryonic cells (hESCs). engineered light-sensitive hESCs through CRISPR-Cas9-mediated integration optoBMP into AAVS1 locus. The activation with blue light, in lieu BMP growth factors, resulted mechanisms upregulation phenotype, significant transcriptional differences compared dark. Furthermore, differentiated light could form pellets consisting hyaline-like cartilaginous matrix. Our findings indicate applicability optogenetics for understanding development engineering.

Язык: Английский

Gradient scaffolds for osteochondral tissue engineering and regeneration DOI

Ziqi Xiong,

Fangyuan Hong,

Zhonglin Wu

и другие.

Chemical Engineering Journal, Год журнала: 2024, Номер 498, С. 154797 - 154797

Опубликована: Авг. 13, 2024

Язык: Английский

Процитировано

7

Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) for modeling cardiac arrhythmias: strengths, challenges and potential solutions DOI Creative Commons

Jyotsna Joshi,

C. Albers,

Nathan Smole

и другие.

Frontiers in Physiology, Год журнала: 2024, Номер 15

Опубликована: Сен. 12, 2024

Ion channels and cytoskeletal proteins in the cardiac dyad play a critical role maintaining excitation-contraction (E-C) coupling provide homeostasis. Functional changes these proteins, whether induced by genetic, epigenetic, metabolic, therapeutic, or environmental factors, can disrupt normal electrophysiology, leading to abnormal E-C arrhythmias. Animal models heterologous cell cultures platforms elucidate pathogenesis of arrhythmias for basic research; however, traditional systems do not truly reflect human electro-pathophysiology. Notably, patients with same genetic variants inherited channelopathies (ICC) often exhibit incomplete penetrance variable expressivity which underscores need establish patient-specific disease comprehend mechanistic pathways determine personalized therapies. Patient-specific pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) inherit background patient electrophysiological characteristics native cardiomyocytes. Thus, iPSC-CMs an innovative translational pivotal platform modeling therapeutic screening. In this review, we will examine how historically evolved model arrhythmia syndromes dish, their utility understanding specific ion functional causing We also CRISPR/Cas9 have enabled establishment patient-independent variant-induced iPSC-CMs-based models. Next, limitations using respect

Язык: Английский

Процитировано

7

Autologous iPSC- and MSC-derived chondrocyte implants for cartilage repair in a miniature pig model DOI Creative Commons
Ming‐Song Lee, Eric Chang-Yi Lin,

Athillesh Sivapatham

и другие.

Stem Cell Research & Therapy, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 23, 2025

Язык: Английский

Процитировано

0

Cell reprogramming: methods, mechanisms and applications DOI Creative Commons
Fei Zhu, Guangjun Nie

Cell Regeneration, Год журнала: 2025, Номер 14(1)

Опубликована: Март 27, 2025

Abstract Cell reprogramming represents a powerful approach to achieve the conversion cells of one type into another interest, which has substantially changed landscape in field developmental biology, regenerative medicine, disease modeling, drug discovery and cancer immunotherapy. is complex ordered process that involves coordination transcriptional, epigenetic, translational metabolic changes. Over past two decades, range questions regarding facilitators/barriers, trajectories, mechanisms cell have been extensively investigated. This review summarizes recent advances mediated by transcription factors or chemical molecules, followed elaborating on important roles biophysical cues reprogramming. Additionally, this will detail our current understanding govern reprogramming, including involvement recently discovered biomolecular condensates. Finally, discusses broad applications future directions development, regenerative/rejuvenation therapy,

Язык: Английский

Процитировано

0

TGFβ family signaling in human stem cell self-renewal and differentiation DOI Creative Commons
Sijia Liu,

Jiang Ren,

Yanmei Hu

и другие.

Cell Regeneration, Год журнала: 2024, Номер 13(1)

Опубликована: Ноя. 28, 2024

Abstract Human stem cells are undifferentiated with the capacity for self-renewal and differentiation into distinct cell lineages, playing important role in development maintenance of diverse tissues organs. The microenvironment provides crucial factors components that exert significant influence over determination fate. Among these factors, cytokines from transforming growth factor β (TGFβ) superfamily, including TGFβ, bone morphogenic protein (BMP), Activin Nodal, have been identified as regulators governing differentiation. In this review, we present a comprehensive overview pivotal roles played by TGFβ superfamily signaling human embryonic cells, somatic induced pluripotent cancer cells. Furthermore, summarize latest research advancements family various cell-based therapy, discussing their potential clinical applications therapy regeneration medicine.

Язык: Английский

Процитировано

2

Role of the TGF-β signaling pathway in induced pluripotent stem cells reprogramming DOI Creative Commons
Weiwen Fan,

Huaibing Yuan,

Le Chang

и другие.

Chinese Medical Journal, Год журнала: 2024, Номер unknown

Опубликована: Июль 22, 2024

To the Editor: The discovery of induced pluripotent stem cells (iPSCs) by Takahashi and Yamanaka in 2006 was hailed as a major breakthrough cell research. And large number experimental studies have proven that transforming growth factor-β (TGF-β) signaling pathway is key iPSC reprogramming. TGF-β can promote or inhibit reprogramming under different conditions [Figure 1]. This article describes role reprogramming.Figure 1: conditions. Akt: protein kinase B; BMP: Bone Morphogenetic Protein; Erk: extracellular signal-regulated kinase; GRB2: factor receptor-bound 2; iPSC: cell; JNK: c-Jun N-terminal Kinase; Klf4: kruppel-like 4; LIMK: Lim-kinase; MEK: mitogen-activated MEKK1: 1; MIS: Müllerian inhibiting substance; MKK:MAP MLC: myosin light chain; MLK3: mixed lineage 3; mTOR: mechanistic target rapamycin; Oct4: octamer-binding transcription PI3K: phosphatidylinositol 3-kinase; p38: p38 Raf: rapidly accelerated fibrosarcoma; Ras: rat sarcoma; RhoA: ras homolog gene family member A; ROCK: Rho-associated ShcA: Src homology 2 domain-containing SOS: son sevenless; Sox2: SRY-box S6K: S6 TAK1: beta-activated TGF-β: Transforming factor-β.According to homology, superfamily be divided into three subfamilies: various subtypes (β1, β2, β3), activin, bone morphogenetic (BMP). transmits signals through receptors, which type I receptors (TβRI)/activin receptor-like (ALK5), II (TβRII), III (TβRIII) according their structural functional properties. TβRI TβRII complex required for signal transduction. Upon binding ligand, catalyzes phosphorylation serine threonine residues guanidine specificity (GS) region TβRI, resulting group downstream molecules called Smads cell. Smad plus general (GTF), other factors, supplementary targets transcription. In addition, TGF-β/BMP cytokines also activate non-Smad molecules. For example, activated induces formation A (ShcA)/growth (GRB2)/son sevenless (SOS) phosphorylating ShcA further activates (ERK)/mitogen-activated (MAPK) Rat sarcoma (Ras)-rapidly fibrosarcoma (Raf)-Mitogen-activated (MEK) pathway; receptor TNF associated 6 (TRAF6) catalyze 1 (TAK1) undergo K63-linked polyubiquitination, then (JNK) (p38 MAPK) via MAP (MKK). induce its bind p85, regulatory subunit phosphoinositide 3-kinase (PI3K), PI3K-protein B (Akt)-mechanistic rapamycin (mTOR) transcriptional regulation. Activated AKT epithelial-mesenchymal transition (EMT) regulation ribonucleoprotein E1. affects activity EMT-triggering pathways, such Notch, Wnt, integrin pathways. Meanwhile, TGF-β-induced regulate signaling. regulates differentiation. TGF-β1 has been shown transformation human-induced (hiPSCs) -derived neural (NSCs) neurons astrocytes vitro. optogenetic modulation precisely control differentiation hiPSCs mesenchymal lineage.[1] It hydrodynamic stress generated shaking culture stimulates chondrogenically iPSCs (CI-iPSCs), promoting chondrogenic mouse Inhibition ability. RepSox displaces (Sox2) ubiquitously expressed cultures containing stable intermediate captured partially reprogrammed state. process, turn, leads sustained Nanog gene, absence Sox2.[2] Moreover, Misaki Yamashita et al[3] found inhibition could human iPSC-derived brain microvascular endothelial-like (iBMELCs) increase proportion endothelial differentiated population. MEK, DNMT, effective inducing enterocytes. Human noncardiomyocyte cardiac (hiPSC-NMCCs) differentiate myofibroblast-like when cultured with transplanted infarcted hearts.[4] Gong al[5] achieve directed hiPSCs-derived crest (NCCs) using chemically defined media glycogen synthesis (GSK-3) inhibitors inhibitors. Indeed, essential maintaining pluripotency (hPSCs). Single-cell RNA sequencing performed Mabrouk al[6] revealed important functions maintenance during early embryonic stages. hPSC, regulator ZNF398 mediates epithelial properties TGF-β. Mechanistically, binds active promoter enhancer SMAD3 histone acetyltransferase EP300, enabling transcription.[7] context somatic reprogramming, disrupts activation well colony formation.[7] hESF 9 medium absolutely dependent on presence TGF-β1. Activin Nodal play roles networks. PI3K activation, EMT/AKT establishes where activin A/SMAD2/3 stimulate self-renewal activating genes, including NANOG. Singh al[8] PI3K/AKT inhibited RAF/MEK/ERK typical Wnt allowing SMAD2/3 pluripotency-related genes NANOG high level undifferentiated state.[8] inhibits mesenchymal-epithelial (MET), an event fibroblasts iPSCs. provides possible mechanism generation Small targeting MET machinery, (SB431542), MEK (PD0325901), ROCK (thiazovivin), alone combination, significantly increased efficiency. According current studies, BMP plays reprogramming: BMP7 percentage colonies four OSKM (OCT4, KLF4, SOX2, c-Myc) (MEFs).[9] Inhibiting enhanced efficiency kinetics OSKM-reprogrammed MEFs, while prevented Considering inhibitor treatment most stages production, it believed exert synergistic effect factors rather than fibroblast transformation. Besides, evidenced therapy replace solitary C-MYC suggests acts bypassing programming SOX2 entirely. Ruetz al[10] showed constitutive increases thereby serving enhance factor-mediated Studies Math6 counteract signaling, affecting initiating steps cellular However, there are still many limitations research specific pathway. instance, remain elusive; this undergoes dynamic changes response conditions; unidentified involved unknown potential understanding participation modulating conclusion, process exploring mechanism, expression changed significantly. mechanisms studied. Funding work supported grants from Key Projects Yunnan Province (No. 202301AY070001-034) Project Provincial Department Education 2023Y0827). Conflicts interest None.

Язык: Английский

Процитировано

1

Optogenetics and Its Transformative Role in Tissue Engineering and Regenerative Medicine DOI Creative Commons
Emine Camcıoglu, Deniz Ghasemi Mohammadrezaloo, Bi̇rcan Di̇nç

и другие.

Nano Select, Год журнала: 2024, Номер unknown

Опубликована: Окт. 27, 2024

ABSTRACT Optogenetics, a revolutionary technique leveraging light stimulation for precise cellular control, holds immense potential in regenerative medicine. Offering unparalleled spatial and temporal accuracy, the entrance of optogenetics into tissue engineering medicine (TERM) empowers researchers to modify genes precisely reversibly, control signal pathways antibodies, as well alter biomaterial properties. Optogenetics provides unprecedented manipulation physiological regeneration, replication intricate developmental processes, laboratory setting. Although further investigation is required safe feasible injection optogenetic systems human bodies, use has already led great amount research on several tissues systems. It found diverse applications TERM skin connective tissue, endothelium, bone, cartilage, muscle; with over vitro or vivo production these tissues, critical proteins pathways, creation light‐controlled wound coverings even tool directional growth living subjects. emerges transformative force shaping future medical science, demonstrating pivotal role advancing paving way innovative therapeutic strategies.

Язык: Английский

Процитировано

1

Recent advancement of sonogenetics: A promising noninvasive cellular manipulation by ultrasound DOI Creative Commons
Jin Bo Tang, M. Feng, Dong Wang

и другие.

Genes & Diseases, Год журнала: 2023, Номер 11(5), С. 101112 - 101112

Опубликована: Сен. 15, 2023

Recent advancements in biomedical research have underscored the importance of noninvasive cellular manipulation techniques. Sonogenetics, a method that uses genetic engineering to produce ultrasound-sensitive proteins target cells, is gaining prominence along with optogenetics, electrogenetics, and magnetogenetics. Upon stimulation ultrasound, these trigger cascade activities functions. Unlike traditional ultrasound modalities, sonogenetics offers enhanced spatial selectivity, improving precision safety disease treatment. This technology broadens scope non-surgical interventions across wide range clinical therapeutic applications, including neuromodulation, oncologic treatments, stem cell therapy, beyond. Although current literature predominantly emphasizes ultrasonic this review comprehensive exploration sonogenetics. We discuss properties, specific employed sonogenetics, technique's potential managing conditions such as neurological disorders, cancer, ophthalmic diseases, therapies. Our objective stimulate fresh perspectives for further promising field.

Язык: Английский

Процитировано

3

Optogenetic manipulation of BMP signaling to drive chondrogenic differentiation of hPSCs DOI Creative Commons
Paul A. Humphreys, Steven Paul Woods, Nicola Bates

и другие.

Cell Reports, Год журнала: 2023, Номер 42(12), С. 113502 - 113502

Опубликована: Ноя. 29, 2023

Optogenetics is a rapidly advancing technology combining photochemical, optical, and synthetic biology to control cellular behavior. Together, sensitive light-responsive optogenetic tools human pluripotent stem cell differentiation models have the potential fine-tune unpick processes by which specification tissue patterning are controlled morphogens. We used an bone morphogenetic protein (BMP) signaling system (optoBMP) drive chondrogenic of embryonic cells (hESCs). engineered light-sensitive hESCs through CRISPR-Cas9-mediated integration optoBMP into AAVS1 locus. The activation with blue light, in lieu BMP growth factors, resulted mechanisms upregulation phenotype, significant transcriptional differences compared dark. Furthermore, differentiated light could form pellets consisting hyaline-like cartilaginous matrix. Our findings indicate applicability optogenetics for understanding development engineering.

Язык: Английский

Процитировано

3