相关实验视频

Updated: Jan 10, 2026

Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry

Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry

Published on: May 17, 2016

调节MyoD1剂量激活了超越肌原分化的替代细胞命运

Oscar N Whitney¹, Gina M Dailey^1,2, Joseph K McKenna¹

¹Department of Molecular Biology, University of California Berkeley, 94720, Berkeley, USA.

bioRxiv : the preprint server for biology

|November 26, 2025

概括

增加转录因子 (TF) 剂量,如MyoD1,出乎意料地抑制了肌肉细胞分化. 相反,它通过改变基因表达促进了自发收缩的肌管的形成.

科学领域:

分子生物学分子生物学
发育生物学发展生物学
遗传学是一个遗传学.

背景情况:

转录因子 (TF) 剂量对于在发育过程中决定细胞命运至关重要.
不同剂量的TF结合对高亲和度与低亲和度目标的影响尚未完全理解.
MyoD1是骨肌肉发育 (肌体发生) 的关键调节者.

研究的目的:

研究转录因子剂量在细胞命运决定中的作用.
检查增加MyoD1剂量如何影响骨肌肉分化.
为了阐明底层的分子机制,由于TF剂量改变了肌体形成.

主要方法:

利用活细胞单分子成像来追踪TF结合动态.
使用CUT&RUN和ATAC-seq进行全基因组染色体可访问性和TF结合分析.
整合RNA-seq数据以将TF结合与基因表达变化相关联.

主要成果:

较高的MyoD1剂量出乎意料地抑制了正规的骨肌肉分化.
增加MyoD1剂量导致非肌原性基因的上调,包括细胞粘附基因.
较高的MyoD1水平促进了与较低亲和度的基因组位点的结合,扩大了目标基因激活.
这导致了自发收缩的神经管的形成,这是一个新的表型.

结论:

转录因子剂量可以通过改变基因调节网络来重新编程发育轨迹.
增加的MyoD1剂量会导致从高亲和度结合点转移到低亲和度结合点,激活更广泛的基因组.
这种依赖于TF剂量的机制揭示了触发不同发育程序的新途径,影响细胞命运决策.

更多相关视频

Exon Skipping in Directly Reprogrammed Myotubes Obtained from Human Urine-Derived Cells

Exon Skipping in Directly Reprogrammed Myotubes Obtained from Human Urine-Derived Cells

Published on: May 7, 2020

Direct Reprogramming of Human Fibroblasts into Myoblasts to Investigate Therapies for Neuromuscular Disorders

Direct Reprogramming of Human Fibroblasts into Myoblasts to Investigate Therapies for Neuromuscular Disorders

Published on: April 3, 2021

相关概念视频

Master Transcription Regulators

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...

Satellite Stem Cells and Muscular Dystrophy

Satellite Stem Cells and Muscular Dystrophy

Satellite stem cells or myosatellite cells are quiescent stem cells that Alexander Mauro first identified in 1961. These cells are located between the sarcolemma, the plasma membrane of muscle fibers, and the basal lamina, the connective tissue sheath covering it. These mononucleated cells are activated in response to muscle injury, can transform into myoblasts, and may form or repair muscle fibers. Myosatellite cells can provide additional myonuclei for muscle regeneration or return to a...

Formation of Muscle Fibers from Myoblasts

Formation of Muscle Fibers from Myoblasts

De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...

Forced Transdifferentiation

Forced Transdifferentiation

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.
Artificial...

Somatic to iPS Cell Reprogramming

Somatic to iPS Cell Reprogramming

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...

Cellular Differentiation

Cellular Differentiation

How does a complex organism such as a human develop from a single cell? It all starts from a single fertilized egg which gives rise to a vast array of cell types, such as nerve cells, muscle cells, and epithelial cells that characterize the adult? Throughout development and adulthood, cellular differentiation leads cells to assume their final morphology and physiology. Differentiation is the process by which unspecialized cells become specialized to carry out distinct functions.
A zygote is a...