Онтогенез, Год журнала: 2023, Номер 54(5), С. 306 - 322
Опубликована: Сен. 1, 2023
Язык: Английский
Cell stem cell, Год журнала: 2024, Номер 31(9), С. 1244 - 1261
Опубликована: Авг. 19, 2024
Язык: Английский
Процитировано
10
Cell Death and Disease, Год журнала: 2024, Номер 15(1)
Опубликована: Янв. 4, 2024
Abstract Effective therapeutics is much needed for amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease mainly affecting motor neurons. By screening chemical compounds in human patient-derived and aging-relevant neurons, we identify a neuroprotective compound show that MAP4Ks may serve as therapeutic targets treating ALS. The lead broadly improves survival function of neurons directly converted from ALS patients. Mechanistically, it works inhibitor MAP4Ks, regulates the MAP4Ks-HDAC6-TUBA4A-RANGAP1 pathway, normalizes subcellular distribution RANGAP1 TDP-43. Finally, mouse model inhibiting preserves significantly extends animal lifespan.
Язык: Английский
Процитировано
5
Biological Theory, Год журнала: 2025, Номер unknown
Опубликована: Янв. 10, 2025
Язык: Английский
Процитировано
0
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(6), С. 3466 - 3466
Опубликована: Март 19, 2024
This study aims to investigate the induction effect of LncRNA-CIR6 on MSC differentiation into cardiogenic cells in vitro and vivo. In addition pretreatment with Ro-3306 (a CDK1 inhibitor), was transfected BMSCs hUCMSCs using jetPRIME. further hearts C57BL/6 mice via 100 μL AAV9-cTnT-LncRNA-CIR6-ZsGreen intravenous injection. After three weeks transfection followed by AMI surgery, (5 × 105/100 μL) were injected intravenously one week later. Cardiac function evaluated VEVO 2100 electric mapping nine days after cell Immunofluorescence, Evans blue-TTC, Masson staining, FACS, Western blotting employed determine relevant indicators. induced a significant percentage (83.00 ± 0.58)% (95.43 2.13)% cells, as determined expression cTnT immunofluorescence FACS. High cTNT observed MSCs blotting. Compared MI group, cardiac contraction conduction treated or combined injection groups significantly increased, areas fibrosis lower. The transcriptional region Chr17 from 80209290 80209536. functional located at nucleotides 0–50/190–255 sequence. CDK1, protein found be related proliferation cardiomyocytes, secondary structure (from 0 17). impeded while showed high CDK1. mediates repair infarcted inducing through
Язык: Английский
Процитировано
3
Molecular Psychiatry, Год журнала: 2022, Номер 28(2), С. 746 - 758
Опубликована: Окт. 7, 2022
Язык: Английский
Процитировано
15
Cells, Год журнала: 2022, Номер 11(21), С. 3435 - 3435
Опубликована: Окт. 31, 2022
The discovery of the skeletal muscle-specific transcription factor MyoD represents a milestone in field transcriptional regulation during differentiation and cell-fate reprogramming. was first tissue-specific found capable converting non-muscle somatic cells into muscle cells. A unique feature MyoD, with respect to other lineage-specific factors able drive trans-differentiation processes, is its ability dramatically change cell fate even when expressed alone. present review will outline molecular strategies by which reprograms origin myogenic conversion, focusing on activation coordination complex network co-factors epigenetic mechanisms. Some roadblocks, restrain MyoD-dependent trans-differentiation, possible ways for overcoming these barriers, also be discussed. Indeed, they are critical importance not only expand our knowledge basic biology but improve generation translational research.
Язык: Английский
Процитировано
10
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Янв. 28, 2024
Abstract Purpose This study aims to investigate the induction effect of LncRNA-CIR6 on MSCs differentiation into Cardiogenic Cells in vitro and vivo . Methods In addition pretreatment with Ro-3306 (CDK1 inhibitor), was transfected BMSCs hUCMSCs using jetPRIME. C57BL/6 mice heart by 100 μL AAV9-cTnT-LncRNA-CIR6-ZsGreen i.v. After 3 weeks transfection followed AMI surgery, (5×10 5 /100 μL) were injected i.v 1 week later. Cardiac function evaluated VEVO 2100 electric mapping 9 days after cell injection. IF, Evans blue-TTC, Masson staining, FACS, WB used determine relevant indicators. Results induced a significant percentage (83.00±0.58)% (95.43±2.13)% cardiogenic cells, as determined expression cTnT. Compared MI group, cardiac contraction conduction treated or combined injection groups significantly increased well area fibrosis lower. The transcriptional region Chr17 from 80209290 80209536. functional located at nucleotides 0-50/190-255 sequence. CDK1 is protein found be related proliferation cardiomyocytes which secondary structure (from 0 17). impeded while showed high CDK1. mediates repair infarcted hearts inducing cells through Conclusions
Язык: Английский
Процитировано
0
Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(39)
Опубликована: Сен. 18, 2024
A number of studies have demonstrated that it is possible to directly convert one cell type another by factor-mediated transdifferentiation, but in the vast majority cases, resulting reprogrammed cells are unable maintain their new identity for prolonged culture times and a phenotype only partially similar endogenous counterparts. To better understand this phenomenon, we developed an analytical approach characterizing trans-differentiation-associated changes DNA methylation, major determinant long-term identity. By examining various models transdifferentiation both vitro vivo, our indicate despite convincing expression changes, transdifferentiated seem alter original developmentally mandated methylation patterns. We propose blockage due basic developmental limitations built into regulatory sequences govern epigenetic programming These results shed light on molecular rules necessary achieve complete somatic reprogramming.
Язык: Английский
Процитировано
0
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown
Опубликована: Апрель 24, 2023
ABSTRACT Effective therapeutics is much needed for amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease mainly affecting motor neurons. By screening chemical compounds in human patient-derived and aging-relevant neurons, we identify a neuroprotective compound show that MAP4Ks may serve as therapeutic targets treating ALS. The lead broadly improves survival function of neurons directly converted from ALS patients. Mechanistically, it works inhibitor MAP4Ks, regulates the MAP4Ks-HDAC6-TUBA4A-RANGAP1 pathway, normalizes subcellular distribution RANGAP1 TDP-43. Finally, mouse model inhibiting preserves significantly extends animal lifespan.
Язык: Английский
Процитировано
1
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown
Опубликована: Май 24, 2022
Abstract Synonymous and noncoding single nucleotide polymorphisms (SNPs) in the KCNJ6 gene, encoding G protein-gated inwardly rectifying potassium (GIRK2) channel subunit 2, have been linked with increased electroencephalographic frontal theta event-related oscillations (ERO) subjects diagnosed alcohol use disorder (AUD). To identify molecular cellular mechanisms while retaining appropriate genetic background, we generated induced excitatory glutamatergic neurons (iN) from iPSCs derived four AUD-diagnosed variants (‘Affected: AF’) control without (‘Unaffected: UN’). Neurons were analyzed for changes gene expression, morphology, excitability physiological properties. Single cell RNA sequencing suggests that AF variant altered patterns of synaptic transmission projection morphogenesis. Results confirm express lower levels GIRK2, greater neurite area, elevated excitability. Interestingly, exposure to intoxicating concentrations ethanol induces GIRK2 expression reverses functional effects neurons. Ectopic overexpression alone mimics effect normalize We conclude decrease increase this can be minimized or reduced ethanol.
Язык: Английский
Процитировано
1