Name: reprogramming cells into stem cells
Uploaded: 2020-11-23T11:47:37.000Z
Duration: 1 min 13 s
Channel: JoVE

被诱导的多能干细胞iPSC
 
 是成熟的分化细胞 例如皮肤细胞
 
 其在实验室中重编程的细胞
 
 为与未分化的胚胎干细胞相似
 
 也就是说 它们会分裂并且是多能的
 
 能够在体内产生任何细胞类型
 
 例如 可用于替换受损视网膜组织的
 
 视网膜细胞
 
 为了产生iPSC
 
 可从患者体内取出成熟细胞
 
 如皮肤成纤维细胞，并进行培养
 
 然后 通常转录因子的基因
 
 通过病毒载体递送到细胞核中
 
 在那里它们被整合到基因组中
 
 转录因子然后打开
 
 由胚胎干细胞表达的基因
 
 这样能将他们分散
 
 并使他们处于多能状态
 
 现在 细胞可以分裂 并且理想情况下
 
 可倒入到培养物中产生特定的细胞类型
 
 然后可以将新细胞
 
 移植回患者体内 以最小的排斥风险
 
 治疗损伤或疾病
 
 因为它们来自患者自身的细胞

Hamazaki、Takashi、Nihal El Rouby、Natalie C. Fredette、Katherine E. Santostefano 和 Naohiro Terada。"简明回顾:精准医学时代的诱导多能干细胞研究。"干细胞（俄亥俄州代顿）35，第 3 期（2017 年 3 月）:545-50。[<a href="https://doi.org/10.1002/stem.2570" target="__blank">来源</a>]。

诱导性多能干细胞

Induced Pluripotent Stem Cells

干细胞是未分化的细胞，分裂并产生不同类型的细胞。通常，分化成特定细胞类型的细胞是有丝分裂后的，也就是说，它们不再分裂。然而，科学家们已经找到了一种方法来重新编程这些成熟细胞，使它们“去分化”并恢复到未分化、增殖状态。这些细胞也是像胚胎干细胞一样的多能干细胞，能够产生所有类型的细胞，因此被称为诱导多能干细胞（IPSC）。

iPSCs在医学上具有潜在的价值，因为患者需要特定的细胞类型，例如，由于黄斑变性而导致视网膜受损的患者可以接受所需细胞的移植，这些细胞是由自身体内的另一种细胞类型产生的。这被称为自体移植，它降低了在个体间移植组织时发生移植排斥反应的风险。
 
<h4>过程</h4>
 
为了制造iPSCs，成熟细胞如皮肤成纤维细胞或人的血细胞在培养中生长。然后，使用病毒载体将多个转录因子的基因传递到细胞中，并使用细胞机器表达转录因子蛋白。转录因子随后启动许多由胚胎干细胞表达的其它基因，使细胞回到未分化、增殖和多能状态。
 
目前仍在研究iPSCs是否真的等同于胚胎干细胞，但它们看起来很相似，可以从身体的所有三个生殖层产生细胞。与其它类型的干细胞一样，科学家正在学习如何有效地促进特定细胞类型与iPSCs的分化，以便能够产生足够数量的所需细胞类型。
 
<h4>早期临床试验</h4>
 
第一个临床试验将来自iPSCs的视网膜细胞移植到年龄相关性黄斑变性患者中。自那以后，iPSC的几个临床试验已经被批准用于治疗帕金森病、心脏病和脊髓损伤。从病人身上提取并转化为 iPSCs的细胞也被用来在实验室研究他们的疾病。一般来说, iPSCs为科学研究提供了另一种干细胞来源。

干细胞是能够分裂并产生不同类型细胞的未分化细胞。通常情况下，已分化为特定细胞类型的细胞……

Education

教育

JoVE Core

Molecular Biology

分子生物学

Unit 1

第一单元

Gene Expression

基因表达

KEY TERMS AND CONCEPTS

关键术语与概念

诱导多能干细胞

reprogramming cells into stem cells

Induced pluripotent stem cells are created by reprogramming mature cells back into a stem-cell state. This process shows that specialized cells can be changed into cells with broader developmental potential. The topic is important in biology because it links cell identity, gene control, and stem cell research.

These cells begin as ordinary body cells and are pushed to de-differentiate, or lose their specialized features. After reprogramming, they behave like pluripotent stem cells, which means they can give rise to many different cell types. That ability makes them useful for studying how cells develop and how cell fate can be changed.

The transcript focuses on induced pluripotent stem cells as a key example of reprogramming rather than on a single tissue source. It highlights how scientists can generate stem-cell-like cells from mature cells in the lab. For high school biology, this topic connects cell specialization with the idea that gene activity can be reset.

Reprogramming Cells into Stem Cells

cell specific gene expression

How Cells Switch Genes On and Off

Cells switch genes on and off to make different proteins for different jobs. In multicellular organisms, many cell types are built from the same DNA, but they do not use the same genes in the same way. This difference in gene expression helps explain why cells can look and act so differently. Liver cells are a clear example. They help detoxify blood, make bile to help digest fats, and produce proteins needed for metabolism. To do these jobs, liver cells must express a specific set of genes.

regulation of expression occurs at multiple steps

regulation-of-expression-occurs-at-multiple-steps

How Cells Control Gene Expression

Cells control gene expression at several points between DNA and protein. The most common control point is transcription. At this stage, proteins bind to short regulatory DNA sequences and can either increase or reduce transcription of the linked gene. After transcription, a precursor mRNA is made. This pre-mRNA contains exons, which code for protein, and introns, which do not. It must be processed before translation, and splicing removes the introns and joins the exons. Cells can also regulate...

cis-regulatory sequences

How Cis-Regulatory DNA Controls Transcription

Cis-regulatory sequences are short, non-coding DNA segments that control gene transcription. They sit on the same chromosome as the genes they regulate and act as binding sites for transcriptional regulators. In eukaryotes, these proteins help control gene expression patterns in different cell types. These DNA sequences can be close to a gene or thousands of bases away. When they are far from the gene in the DNA sequence, they are often brought close together in space because chromosomes are...

cooperative binding of transcription regulators

cooperative-binding-of-transcription-regulators

How Transcription Factors Bind DNA

Transcriptional regulators bind to cis-regulatory DNA sequences to control gene transcription. These DNA sequences are very short, usually fewer than ten nucleotide pairs long. Because they are so short, the same sequence can appear by chance in many places across the genome. Some regulators can also bind to groups of similar sequences. That raises the chance of random binding even more. To lower this risk, transcription regulators often form dimers, which are pairs of proteins that bind a DNA...

prokaryotic transcriptional activators and repressors

prokaryotic-transcriptional-activators-and-repressors

Operon Control by Activators and Repressors

Operon control in prokaryotes depends on activators and repressors. Prokaryotic genes are often arranged in groups, not one by one like in eukaryotes. Genes that help carry out the same biochemical process are placed together with their regulatory elements. This group is called an operon, and it is transcribed into a single polycistronic mRNA strand. Activators and repressors are DNA-binding proteins that control transcription in an operon. Activators bind near the promoter, which is the site...

operons

Operons in Bacterial Gene Control

Operons help bacteria control groups of genes at the same time. An operon is a set of genes that are regulated together and can be turned on or off as a unit. This shared control helps bacteria respond quickly to changes in their environment. In many operons, a promoter gives RNA polymerase a place to bind and start transcription. The operon also includes a regulatory region that helps control whether the genes are expressed. When conditions change, the cell can use this setup to manage gene...

the eukaryotic promoter region

Eukaryotic Promoter Motifs and Gene Control

The eukaryotic promoter region is a stretch of DNA located upstream of a gene. It includes an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences. These DNA signals help control when transcription begins. The promoter can be divided into proximal and distal regions. The proximal promoter lies close to the gene and includes cis-regulatory sequences and the core promoter. The core promoter is the RNA polymerase binding site, and it is usually found...

co-activators and co-repressors

Chromatin Control in Gene Transcription

Chromatin control plays a major role in gene transcription in eukaryotes. Gene expression is regulated by several proteins that work together at a gene regulatory site. Some of these proteins bind directly to specific DNA sequences, while co-regulators attach to those regulators but do not bind DNA on their own. Co-regulators can act as co-activators or co-repressors, depending on the complex they join. One co-regulator may even switch roles in different settings. For example, the...

eukaryotic transcription activators

How Transcription Activators Turn Genes On

Transcription activators are proteins that help turn genes on by promoting transcription from DNA to RNA. They often have two parts. One part binds to DNA, and the other part activates transcription. In some proteins, such as the glucocorticoid receptor and MyoD, one domain can do both jobs. The DNA-binding part recognizes specific regulatory sequences on the DNA. These binding domains are grouped into families based on their structure. Common examples include the leucine zipper, zinc finger,...

eukaryotic transcription inhibitors

How Eukaryotic Gene Repressors Work

Eukaryotic gene repressors help turn specific genes off when the cell needs to control growth, development, or other biochemical processes. These DNA-binding proteins regulate gene expression in eukaryotes. Their presence at the right time and place can be triggered by hormones and signals from other cells. Most transcription inhibitors have two main parts. One part binds DNA, and the other is a repressor domain, which helps shut down transcription. Repressor domains can connect with basal...

combinatorial gene control

Gene Expression by Transcription Factor Combinations

Gene expression can depend on combinations of transcription factors working together. In combinatorial gene control, several transcription factors act in a coordinated way to regulate a single gene. If one or more of these factors are missing, the level of gene expression or repression can change a lot. This kind of control helps explain how a relatively small number of transcription factors can regulate a very large number of genes. More than 30,000 genes are controlled by about 2,000 to...

induced pluripotent stem cells

Induced pluripotent stem cells are created by reprogramming mature cells back into a stem-cell state. This process shows that specialized cells can be changed into cells with broader developmental potential. The topic is important in biology because it links cell identity, gene control, and stem cell research. These cells begin as ordinary body cells and are pushed to de-differentiate, or lose their specialized features. After reprogramming, they behave like pluripotent stem cells, which means...

master transcription regulators

MEF2C and Gene Control Cascades

MEF2C is a master transcription regulator that controls gene expression in coordinated cascades. These regulators are proteins that manage the activity of multiple genes that often work together to produce a complex outcome. When a master transcription regulator is activated, it can start a chain of transcriptional activation that supports that outcome. Master transcription regulators can act in two main ways. They may bind directly to the regulatory sequences of several genes involved in a...

epigenetic regulation

DNA Methylation and Histone Changes

Epigenetic regulation controls gene activity without changing the DNA sequence. It helps determine when genes are turned on or off in a cell. Two major epigenetic mechanisms are DNA methylation and histone modification. DNA methylation adds chemical groups to DNA, while histone changes affect how tightly DNA is packed around histone proteins. These changes can make genes easier or harder to use. In high school biology, epigenetic regulation is important for understanding how cells with the...

genomic imprinting and inheritance

Genomic Imprinting in Human Disease

Genomic imprinting affects how some inherited genes are turned on or off in human cells. Diploid organisms inherit chromosomes from both parents, and each gene usually has two alleles. In most cases, both alleles are expressed. If one allele is missing or mutated, the other can often compensate, but some genes do not work that way. In genomic imprinting, a gene or its regulatory sequence carries chemical tags, such as methyl groups, on the copy inherited from only one parent. These tags are...

key terms and concepts

Learn how mature cells can be reprogrammed into induced pluripotent stem cells and why de-differentiation matters in stem cell biology.

Reprogramming Cells into Stem Cells | JoVE K12

molecular biology

JoVE Core 分子生物学通过清晰简洁的动画视频课程展示了细胞的分子过程。此外，在科学家在行动的视频中，这些概念的应用是通过现代实验室中的真实实验演示的。

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Reprogramming Cells into Stem Cells

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