Eddie the Enterocyte By Jennifer A.

Markovics Deep inside the gut of a young girl, in the epithelial lining of her small intestine, there once lived a very unusual cell named Eddie the Enterocyte. It was an ordinary day when Eddie came into being by asymmetric division from the mother stem cell in the depths of the crypt. Immediately upon the completion of this division, Eddie felt his whole cell begin to change the membrane on one side of him began to grow out with little hair-like projections into the lumen, while his nucleus moved closer to the other end of his cell, towards the underlying basal lamina. Then he felt a shove from the neighboring cell that was just being born, itself, by asymmetric division from the stem cell. Eddie was being shoved up into another cell on his other side. Amongst all of this commotion, Eddie noticed a different kind of cell with a long extended body, unlike Eddie and his neighboring cells columnar bodies. This cell migrated towards Eddie from beneath the basal lamina. When it reached Eddie, it stopped and started secreting all sorts of factors at him. Eddie just stared blankly at these factors. The fibroblast looked sternly at Eddie, You better eat this stuff, Im not secretin it for nothin! Eddie did not understand. Why? What is this stuff? The fibroblast was surprised by Eddies unusual response. Most cells just ate the factors without question. This stuff is supposed to make you grow - theyre a bunch of different types of growth factors! Protein ligands, neurotransmitters, cytokines, whatever. Theyll signal directly or indirectly down to your nucleus to make you into a functioning enterocyte by the time you get up into the villus. Eddie was bewildered. Whats an enterocyte? The fibroblast just shook its cytoplasmic extension and stopped secreting for a moment. Enterocytes are the major absorptive cells of the intestine. As an enterocyte, you control the absorption of nutrients into the body, thereby supplying the rest of us cells with energy to live. My job is to help you become an enterocyte and to help you with your migration to the top of the villus. Eddie thought for a moment. So Im really important, huh? Eddies apical cytoplasm began to enlarge with pride. He took a bite of some growth factors. They tasted good, so he gobbled up more. You can thank me for that! The fibroblast growled. Yeah, thanks, whatever Eddie mumbled ungratefully. Eddie felt things churning inside him, his cytoplasm was busy transducing the signals from eating the growth factors, his nucleus busy transcribing new enterocyte-specific genes, exporting the transcripts into the cytoplasm for translation into proteins by ribosomes, some of which were in the membrane of the endoplasmic reticulum, getting ready for secretion. He was turning into an enterocyte. He smiled with pride. Then, Eddie burped out some factors towards the fibroblast. Finally! I thought youd never secrete me anythin! The fibroblast quickly extended itself and endocytosed the factors. Eddie found himself being shoved again. Thats when he noticed on his apical side that there was something else approaching an opening of some sort. He turned to look at the fibroblast again. Hey, are we at the villus?

Yes, were just about there. Eddie sighed with relief. Im so glad, then theyll stop pushing me! The fibroblast laughed. hahaha! No! They wont stop til youre at the top of the villus! What will I do then? Youll be extruded into the lumen where youll die by anoikis. WHAT?!?! Eddie was astonished! Whats anoikis? And why will I die? Anoikis is the type of programmed cell death that happens when a cell loses contact with another cell. Thats why youll die, cause youll lose contact with your neighboring cells cause theyll shove you right out into the lumen. The fibroblast saw that Eddie was upset. It made him uncomfortable. Look, I dont know whyIm just doin my job here. The fibroblast secreted more growth factors and looked away. Suddenly, Eddie did not feel like being an enterocyte anymore if that meant he had to die. Then he had a thought. Well, what about the mother stem cell? Does she ever die? It was apparent to the fibroblast now that Eddie was not at all like the other enterocytes it had helped to the tip. No, of course not. The stem cells job is to keep dividing and making all the epithelial cells of the intestine. Eddie had an idea. He stopped eating the growth factors. Im gonna be a stem cell then! He announced. Just as Eddie and the fibroblast reached the bottom of the villus, Eddie began his first division. As Eddie exited growth arrest and entered the first growth period of the cell cycle, the fibroblast pleaded with him not to do it. Please, Eddie, were at the base of the villus its time for you to start absorbing! But Eddie ignored the fibroblast, and, passing the G1/S phase checkpoint, he entered into the synthesis phase and his DNA began to be replicated in the nucleus. Eddie! The fibroblast cried, but it was too late. Now Eddie had two times his normal amount of DNA and must either finish dividing or kill himself by apoptosis, another form of programmed cell death.

And so it went. Eddie began dividing, but, unlike the stem cell, his divisions were symmetric and therefore all of his progeny were exactly like himself. They were all enterocytes, or supposed to be enterocytes, and all were as stubborn and selfish as Eddie. They also decided to continue dividing. Soon, the epithelium was very crowded and the enterocytes were unable to migrate fast enough up and out of the tip of the villus. The cells began to pile up on top of each other. Instead of the single layer of cells between the lumen and the basal lamina which normally exists, now there were multiple layers of cells. The cells closest to the lumen were not in contact with the fibroblasts, and were thus getting weaker because they were not getting the growth factors they needed. The cells closest to the basal lamina, although well fed by the fibroblasts, were uncomfortable, squished and angry. After many days of constantly dividing, Eddie was flattened between many clones of himself on one side and the basal lamina on the other. He had long-since lost his columnar shape and was even beginning to resemble the shape of his old friend, the fibroblasts, who had left many days ago to find help. He had returned with an army of lymphocytes and leukocytes and they began a battle. The lymphocytes identified altered cells while the leukocytes secreted killer enzymes to kill off some cells, but the Eddie clones were only getting smarter, their DNA changing so that they

could divide even faster, outnumbering the army of leukocytes. All of this commotion only upset Eddie more. It was time to move on, he thought but not up the villus tip just to die! Then, Eddie spotted where the lymphocytes and leukocytes were coming from a large red vessel that traveled up the stalk of the villus. Thats where Ill go, he decided. First, Eddie secreted some proteolytic enzymes to degrade the basal lamina. Then, remembering how the fibroblast moved, Eddie extended a foot-like shape of cytoplasm and surrounding membrane into the hollow. Quickly getting the feel for migration, he moved slickly through the mesenchyme. As he reached the red vessel, he noticed it was actually made up of cells. What kind of cell are you? asked Eddie to one of these cells. Eddie was surprised by the small, yet cheerfully pleasant voice that responded. Oh, Im an endothelial cell, he said enthusiastically. The other endothelial cells and I form the blood vessels by lining up and connecting a large hole in the middle of our cells. Do you wanna come inside? Then it moved aside and let Eddie slip in between it and an adjacent endothelial cell into the liquid-filled vessel. Suddenly, Eddie was pulled up with the current and noticed many small, disc-like red cells flying past. As Eddie was larger, he moved more slowly, but it was still very fast for Eddie. Then, he felt himself being pulled into a new, larger vessel where the movements were broken up into forceful pulses. With each pulse, Eddie would tumble and flip. Soon he was very dizzy and sick. He decided that he needed to get out of the vessel as soon as possible. As soon as Eddie decided he needed to stop, one final pulse shot him out into a narrow canal where the current was much slower. Here, he relaxed in the more comfortable pace, but soon found himself skidding up against some large, cuboidal cells that were trying to exchange things with him. Hey you got some toxins, some biproducts, some gases? The large, cuboidal cell asked Eddie. It held onto Eddie through some strong receptors. What? Eddie was confused. The large cuboidal cell looked at it with curiosity. Hey, youre not a blood cell! Where did you come from? Um Eddie thought about what the fibroblast had told him, the intestine? Oh, man! The large cell grabbed Eddie out of the canal and pulled him beside it. Look, youre gonna mess this whole place up, you cant be in there. Just sit beside me for now, ok? The large, cuboidal cell seemed like the kind of cell you did not want to mess with so Eddie just did as he was told and just sat beside it. After awhile, Eddie started to feel hungry. He turned to the busy, large, cuboidal cell, Hey, Im hungry, do you know where I can get some factors? The large, cuboidal cell did not look at Eddie and kept working, but answered, Look, buddy, were all hungry! There arent many factors goin around lately. I dont know whats up, but some of my friends have even gotten so sick they cant work! And you know what? What? Eddie was a little intimidated by the large, cuboidal cell. I think its you cells over in the intestine not doin your job! Now the cuboidal cell turned to look at Eddie, but he kept on exchanging with the blood. I heard you all been messin around down

there. And now look at you! You came here to screw us up, too! Well, I wont let you! Then the cell looked back at what it was doing. Eddie felt awful. He thought for a moment about how he might be able to fix things. Then it hit him. Hey, why dont you just divide and make more cells just like you? The hepatocyte stopped for a moment. Then he kept working. Hmmmthats not such a bad idea. And so again, thats how it went. The hepatocyte followed Eddies suggestion and began to make more of itself. But it couldnt keep doing its work, so toxins were not being broken-down and biproducts were drifting through the bloodstream to the rest of the body. As the cells got sicker, Eddie and the hepatocytes divided more. Soon, the surrounding, normal cells were dying off left and right. Then, one gloomy day, the cancer had gotten so bad that the little girls body gave out and she died. The End.