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

Indukowane pluripotencjalne komórki macierzyste, iPSC, to dojrzałe, zróżnicowane komórki, takie jak komórki skóry, które są przeprogramowywane w laboratorium tak, aby były podobne do niezróżnicowanych embrionalnych komórek macierzystych. Oznacza to, że dzielą się i są pluripotencjalne, zdolne do wytwarzania dowolnego typu komórek w organizmie. Na przykład komórki siatkówki, które można wykorzystać do zastąpienia uszkodzonej tkanki siatkówki.

Aby wytworzyć iPSC, dojrzałe komórki, takie jak fibroblasty skóry, są pobierane od pacjenta i umieszczane w hodowli. Następnie, zazwyczaj, geny czynników transkrypcyjnych są dostarczane przez wektory wirusowe do jąder komórkowych, gdzie są włączane do genomu.

Czynniki transkrypcyjne włączają następnie geny, które ulegają ekspresji przez embrionalne komórki macierzyste. Skutecznie, odróżnicowując je i doprowadzając do stanu pluripotencjalnego.

Komórki mogą się teraz dzielić, a najlepiej być kierowane w celu wytworzenia określonego typu komórek w hodowli. Nowe komórki mogą być następnie przeszczepione z powrotem do pacjenta w celu leczenia uszkodzeń lub choroby przy minimalnym ryzyku odrzucenia, ponieważ pochodzą z własnych komórek pacjenta.

Hamazaki, Takashi, Nihal El Rouby, Natalie C. Fredette, Katherine E. Santostefano i Naohiro Terada. "Zwięzły przegląd: Indukowane badania pluripotencjalnych komórek macierzystych w erze medycyny precyzyjnej". Stem Cells (Dayton, Ohio) 35, nr 3 (marzec 2017): 545–50. [<a href="https://doi.org/10.1002/stem.2570" target="__blank">Źródło</a>].

indukowane pluripotencjalne komórki macierzyste

Induced Pluripotent Stem Cells

Komórki macierzyste to niezróżnicowane komórki, które dzielą się i wytwarzają różne typy komórek. Zwykle komórki, które różnicowały się w określony typ komórek, przechodzą proces postmitotyczny“co oznacza, że nie dzielą się już. Naukowcy znaleźli jednak sposób na przeprogramowanie tych dojrzałych komórek, tak aby “odróżnicowały się” i powróciły do niewyspecjalizowanego stanu proliferacyjnego. Komórki te są również pluripotencjalne, podobnie jak embrionalne komórki macierzyste — zdolne do wytwarzania wszystkich typów komórek — i dlatego nazywane są indukowanymi pluripotencjalnymi komórkami macierzystymi (iPSC).

Komórki iPSC są potencjalnie cenne w medycynie, ponieważ pacjent potrzebujący określonego typu komórek — na przykład ktoś z uszkodzoną siatkówką w wyniku zwyrodnienia plamki żółtej — może otrzymać przeszczep wymaganych komórek, wygenerowanych z innego typu komórek w jego własnym organizmie. Nazywa się to przeszczepieniem autologicznym i zmniejsza ryzyko odrzucenia przeszczepu, które może wystąpić w przypadku przeszczepiania tkanek między osobami.

<h4>Proces</h4>

Aby wytworzyć iPSC, w hodowli hoduje się dojrzałe komórki, takie jak fibroblasty skóry lub komórki krwi danej osoby. Następnie geny wielu czynników transkrypcyjnych są dostarczane do komórek za pomocą wektora wirusowego, a białka czynników transkrypcyjnych ulegają ekspresji przy użyciu maszynerii komórkowej. Czynniki transkrypcyjne następnie włączają wiele innych genów ulegających ekspresji w embrionalnych komórkach macierzystych, przywracając komórki do stanu niezróżnicowanego, proliferacyjnego i pluripotencjalnego.

Nadal bada się, czy iPSC są rzeczywiście równoważne embrionalnym komórkom macierzystym, ale wydają się podobne i mogą wytwarzać komórki ze wszystkich trzech listków zarodkowych organizmu. Podobnie jak w przypadku innych typów komórek macierzystych, naukowcy uczą się, jak skutecznie promować różnicowanie określonych typów komórek od iPSC, aby można było wytwarzać potrzebne typy komórek w odpowiednich ilościach.

<h4>Wczesne badania kliniczne</h4>

W pierwszym badaniu klinicznym przeszczepiono komórki siatkówki pochodzące z iPSC pacjentom ze zwyrodnieniem plamki związanym z wiekiem. Od tego czasu zatwierdzono kilka badań klinicznych iPSC w leczeniu choroby Parkinsona, chorób serca i uszkodzeń rdzenia kręgowego. Komórki pobrane od pacjentów i przekształcone w iPSC są również wykorzystywane do badania ich chorób w laboratorium. Ogólnie rzecz biorąc, iPSC stanowią kolejne źródło komórek macierzystych do badań naukowych.

Indukowane pluripotencjalne komórki macierzyste

Komórki macierzyste to niezróżnicowane komórki, które dzielą się i wytwarzają różne typy komórek. Zwykle komórki, które zróżnicowały się w określoną komórkę ...

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JoVE Core

Molecular Biology

Biologia molekularna

Unit 1

Jednostka 1

Gene Expression

Ekspresja genów

KEY TERMS AND CONCEPTS

Kluczowe terminy i pojęcia

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

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Reprogramming Cells into Stem Cells

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