Name: intestinal stem cells and gut lining repair
Uploaded: 2023-04-30T12:09:09.000Z
Duration: 1 min 23 s
Channel: JoVE

The lining of the small intestine is a single layer of epithelial cells divided into two regions. The upper region consists of finger-like projections called villi, and the lower region contains proliferative crypts.&#160;&#160;&#160;
The bottom of the crypt contains undifferentiated intestinal stem cells or ISCs distributed between the differentiated Paneth cells. Lgr5 receptor expression distinguishes these ISCs from the surrounding cells.&#160;
Paneth cells produce localized Wnt&#160; signals that play an essential role in the maintenance and proliferation of ISCs.
The other surrounding niche cells release R-spondin. R-spondin binds to the Lgr5 receptor and enhances the intracellular Wnt signaling.&#160;
The pathways triggered by Wnt ligands and R-spondin lead to the division of ISCs and upward migration of the daughter cells. The daughter cells then divide further and start differentiating into transit-amplifying or TA cells.
TA cells then terminally differentiate into four cell types. The absorptive, goblet, and enteroendocrine cells move to the villus, and the Paneth cells migrate to the crypt.

renewal of intestinal stem cells

Renewal of Intestinal Stem Cells

The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt&#8211; a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells&#8211; the enterocytes or secretory cells&#8211; including the goblet, entero-endocrine, and Paneth cells.
The differentiated cells have distinct functions. Absorptive cells or enterocytes comprise 90% of the intestinal epithelial cell population. They are involved in the absorption and transport of nutrients and electrolytes. Goblet cells secrete mucus which protects the intestinal mucosa. The enteroendocrine cells secrete hormones that help in cell proliferation and digestive activities. Paneth cells secrete antibacterial proteins such as lysozyme and are also involved in the proliferation of stem cells.
Intestinal stem cell proliferation and migration were determined using a labeling method in which radioactive thymidine was injected into the experimental mice&#39;s gut tissues. The actively dividing cells incorporate the radioactive thymidine into their DNA during S-phase. When the same cell divides, the intensity of the label gets reduced as it is distributed between the new daughter cells, which can then be quantified. Based on this experiment, it was found that the rapidly dividing cells, also known as transit-amplifying cells, are present in the middle and upper parts of the crypt, and the slowly dividing stem cells are present in the bottom part of the crypt placed between the Paneth cells. The differentiated mature epithelial cells, except for Paneth cells, are present at the finger-like projections or villi.
Two models were proposed for the identity and location of ISCs&#8211; the stem cell zone model and the +4 cell model. Cheng and Leblond proposed the stem cell zone model in which they found that stem cells are interspersed between the Paneth cells. They named these cells &#8216;crypt base columnar&#8217; or CBC cells. Chris Potten and colleagues proposed the +4 stem cell model. Using the DNA labeling method, they found that these cells are located at the 4th position from the Paneth cells, hence the name &#8216;+4 cells&#8217;.
Recent studies have shown that the CBC cells are the ISCs that participate in renewing intestinal epithelium, whereas the +4 cells are quiescent and become activated upon injury or stress. In such cases, the +4 cells give rise to progenitor cells that eventually replace the cells damaged by stress.

The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the ...

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JoVE Core

Cell Biology

Unit 1

Stem Cell Biology And Renewal in Epithelial Tissue

stem-cell-biology-and-renewal-in-epithelial-tissue

KEY TERMS AND CONCEPTS

intestinal stem cells and gut lining repair

Intestinal stem cells help repair and replace the gut lining every 4 to 5 days. They sit at the base of the crypt, a gland at the bottom of each villus. From this niche, they divide asymmetrically to make one new stem cell and one progenitor daughter cell.

The daughter cells are called transit-amplifying, or TA, cells. They move upward through the crypt and then mature into absorptive cells or secretory cells. The secretory group includes goblet cells, enteroendocrine cells, and Paneth cells.

Each mature cell type has a different job in the intestine. Enterocytes, the absorptive cells, make up about 90% of the intestinal epithelial cell population. They absorb and transport nutrients and electrolytes. Goblet cells release mucus that protects the intestinal mucosa. Enteroendocrine cells secrete hormones that help control cell proliferation and digestive activities. Paneth cells release antibacterial proteins such as lysozyme, and they also support stem cell proliferation.

Scientists studied intestinal stem cell proliferation and migration with a radioactive thymidine label. The label was injected into the gut tissues of experimental mice. Actively dividing cells took up the thymidine into their DNA during S phase. As those cells divided, the label became less intense in the daughter cells and could be measured.

This method showed that TA cells divide quickly in the middle and upper crypt. It also showed that slowly dividing stem cells are found at the bottom of the crypt between Paneth cells. Most mature epithelial cells, except Paneth cells, are located on the villi, the finger-like projections of the intestine.

Two models were proposed for where intestinal stem cells are found. Cheng and Leblond described the stem cell zone model and identified crypt base columnar, or CBC, cells between Paneth cells. Chris Potten and colleagues proposed the +4 stem cell model and placed these cells at the fourth position from the Paneth cells. Recent studies show that CBC cells renew the intestinal epithelium, while +4 cells stay quiet unless there is injury or stress. When activated, +4 cells can produce progenitor cells that help replace damaged cells.

Intestinal Stem Cells and Gut Lining Repair

intestinal-stem-cells-and-gut-lining-repair

zygotic development and stem cell formation

zygotic-development-and-stem-cell-formation

From Zygote to Blastocyst Stem Cells

Zygote development shows how a fertilized egg becomes the first stages of a new organism. When sperm and egg fuse, they form a diploid zygote. A zygote is totipotent, which means it can develop into a complete organism. The zygote then divides by cleavage to form an 8-cell mass. At this stage, the cells are still spherical, loosely attached, and totipotent. Totipotent cells can form both embryonic tissues and extraembryonic tissues. As division continues, the cells reach the 64-cell stage...

source and potency of stem cells

Stem Cell Potency and Development

Stem cells are undifferentiated cells with strong self-renewal ability. They help keep cell populations stable during fetal and adult life. They can also specialize into the cell types of the human body. Their developmental potential varies, so they are grouped into five types: totipotent, pluripotent, multipotent, oligopotent, and unipotent. The fertilized egg, or zygote, is a totipotent stem cell. It can form both embryonic tissues and extraembryonic tissues. As the zygote divides again and...

stem cell niche

How Stem Cell Niches Control Cell Fate

Stem cell niches control how stem cells stay active, rest, or begin to specialize. A niche is the local microenvironment where stem cells live. In this setting, stem cells can remain undifferentiated, renew themselves, or become lineage-specific progenitor cells. Stem cells do not work alone in a niche. They sit next to stromal cells and connect with the extracellular matrix, or ECM, the support network outside the cells. Cell-to-cell and cell-to-matrix signals move through adhesion molecules...

Intestinal stem cells help repair and replace the gut lining every 4 to 5 days. They sit at the base of the crypt, a gland at the bottom of each villus. From this niche, they divide asymmetrically to make one new stem cell and one progenitor daughter cell. The daughter cells are called transit-amplifying, or TA, cells. They move upward through the crypt and then mature into absorptive cells or secretory cells. The secretory group includes goblet cells, enteroendocrine cells, and Paneth cells. <br...

role of ephrin-eph signalling in intestinal stem cell renewal

role-of-ephrin-eph-signalling-in-intestinal-stem-cell-renewal

Ephrin-Eph Signalling in Gut Cell Positioning

Ephrin-Eph signalling helps intestinal cells stay in the right place as the gut lining renews itself. Eph receptors and their Ephrin ligands were first found in a human carcinoma cell line, which is how they got their names. This signalling system is also important in the immune system because it supports immune cell migration, adhesion, and activation. Eph receptors are grouped into two classes, EphA and EphB. Ephrins are also divided into two groups, EphrinA and EphrinB. EphrinA ligands...

role of notch signalling in intestinal stem cell renewal

role-of-notch-signalling-in-intestinal-stem-cell-renewal

Notch Signaling in Gut Stem Cell Fate

Notch signaling helps control how intestinal stem cells renew and decide what cell type to become. In the intestine, this pathway acts through Atoh1, also called atonal homolog 1. Atoh1 pushes cells to become secretory cells. When Notch signaling is active, it limits Atoh1 and keeps the stem cell pool balanced. This pathway depends on direct contact between neighboring cells. It begins when a Notch ligand binds to a receptor on an adjacent cell, which is called trans-binding. If the ligand...

renewal of skin epidermal stem cells

Epidermal Cell Turnover and Repair

The epidermis, the outer layer of skin, is constantly renewed as old cells are replaced by new ones. Skin is organized into three layers: the epidermis, dermis, and hypodermis. In this process, epidermal stem cells, or EpiSCs, divide and make the cells needed to maintain the surface. Some EpiSCs keep self-renewing so the stem cell pool stays active. Others become transit-amplifying, or TA, cells. These cells later form prickle or spinous cells, then granular cells, and finally dead keratinized...

multipotency and niche of bulge stem cell

multipotency-and-niche-of-bulge-stem-cell

Hair Follicle Bulge and Stem Cell Cycles

The hair follicle bulge is the stem cell niche that helps control hair growth and renewal. A hair follicle is a small part of the skin that produces the hair shaft. Paul Gerson Unna was the first to observe the bulge in the outer root sheath, or ORS. The bulge sits between the sebaceous gland and the arrector pili muscle. It houses hair follicle stem cells, or HFSCs, and it also serves as a niche for melanocyte stem cells. When melanocyte stem cells are lost, hair can turn gray. HFSCs express...

clinical applications of epidermal stem cells

clinical-applications-of-epidermal-stem-cells

How Epidermal Stem Cells Aid Skin Repair

Epidermal stem cells help the skin repair minor injuries and replace dead skin cells. These cells are found mainly in the basal layer of the epidermis, the outer layer of skin. For severe wounds, such as major burns or skin damage linked to diabetes or inherited disorders, the body may need help beyond its own repair system. In these cases, epidermal stem cells can be grown from the patient in the lab. Skin taken from an unaffected area can be used to make cultured epidermal autografts, or...

distinctive features of adult stem cells vs cancer stem cells

distinctive-features-of-adult-stem-cells-vs-cancer-stem-cells

Adult and Cancer Stem Cell Traits

Adult stem cells and cancer stem cells share the ability to renew and make specialized cells, but they behave differently in the body. Adult stem cells are unspecialized cells that can divide as needed and, under the right conditions, become specialized cells. Cancer stem cells are a small group of cells inside tumors that also renew and differentiate. Adult stem cells are tissue-specific, which means they help build the tissue where they are found. For example, epithelial stem cells give rise...

stem cell culture

Stem Cell Sources and Therapy

Stem cells can help the body replace damaged cells and repair tissues. Most adult cells lose some ability to divide and heal as they age. Stem cells are different because they do not have a fixed shape or one set job. Adult stem cells are a small group of cells in many tissues, and they keep dividing while also making specialized cells for that same tissue. Scientists still do not fully understand how an unspecialized cell becomes a specialized one. In the lab, stem cells can be pushed to...

tissue renewal without stem cells

Liver and Pancreas Renewal by Cell Division

Liver and pancreas tissues can renew themselves through cell division, even when stem cells are not the main repair source. After tissue damage, some organs rely on resident stem cells to help rebuild lost cells. In the liver and pancreas, however, pre-existing cells can also take part in repair. Pancreas beta cells and liver hepatocytes are two key examples. Beta cells in the pancreas and hepatocytes in the liver can divide to replace cells and regenerate tissue. This process depends on...

unrenewable cells

Permanent Damage to Eye and Ear Cells

Permanent damage to eye and ear cells can affect vision and hearing because some sensory cells cannot be replaced. In humans, the photoreceptor cells of the eye and the sensory hair cells of the ear lack stem cells. That means these cells are unrenewable, so they cannot be replaced after they are damaged or destroyed. The retina contains specialized photoreceptors called rods and cones. These cells change membrane potential when they are stimulated by light energy. Rods and cones differ in the...

key terms and concepts

Learn how intestinal stem cells renew the gut lining, form TA cells, and support villi cell replacement with CBC and +4 stem cell models.

Intestinal Stem Cells and Gut Lining Repair | JoVE K12

cell biology

JoVE Core Cell Biology illustrates complex cellular processes in easy-to-understand yet comprehensive animated video lessons. This collection focuses on the essential components and functions of cells, including organelles and membranes, cellular transport, and cell energetics. It is complemented by scientist-in-action videos that demonstrate the application of cell biology in real-world research experiments.

Intestinal Stem Cells and Gut Lining Repair

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