Chapter 449 Two key genes

"The expression of the MLLT3 gene is the key to determining the self-renewal ability of hematopoietic stem cells."

Ding Mian stood in front of the operating table filled with various equipment, pointed at the bright red in the rectangular petri dish in front of him, and introduced it eloquently.

"This is the result of our hard work for more than half a year, real artificial blood."

"We took epithelial cells from more than ten experimental mice and introduced a combination of four factors, Oct4, Sox2, Nanog and LIN28, to induce all of them into induced pluripotent (iPS) stem cells."

"Following this, five special transcription factors were introduced to induce the iPS stem cells into hematopoietic stem cells."

"Up to this point, the systematic laboratory training I have received is just basic operations, which are quite easy. I think back then, I did such experiments countless times in my doctoral laboratory. I am so familiar with them.

Flow, that's all..."

"Ahem~" Tang Que stood behind him, coughed twice, and said expressionlessly: "Let's get to the point."

"Yes, yes, the focus is on the MLLT3 gene. We used gene editing technology to insert the active MLLT3 gene into the hematopoietic stem cells. Subsequently, the hematopoietic stem cells in the culture dish multiplied at least 20 times and showed no tendency to stop."

"We have transplanted this type of hematopoietic stem cells into mice for testing. The mice developed a fully functional and long-lasting blood system in addition to all the normal components of the immune system, with no signs of leukemia or any other blood disease. This way

The results are enough to confirm the success of the experiment.”

"However, this is only half the battle."

There were about twenty staff members in white coats standing around, their eyes shining, listening attentively.

After being reminded, Ding Mian stopped talking and went straight to the topic.

"Since what we want in addition to hematopoietic stem cells is real artificial blood, we quickly started the next step."

"This has to talk about another H gene that controls blood type."

"As we all know, the antigens expressed on the red blood cell membrane determine the blood type, the most important of which is the ABO blood group system."

"Type O red blood cells do not contain A and B antigens, but the plasma contains anti-A and anti-B antibodies; type A red blood cells have type A antigens on their membranes, and plasma contains anti-B antibodies; type B red blood cells have type B antigens on their membranes

,lAnd the plasma contains anti-A antibodies.”

"Type AB red blood cells have type A and type B antigens on their membranes, but no antibodies are present in the plasma. Any red blood cells of the ABO blood group can be accepted."

"If the wrong blood type is entered and the antigens on the surface of red blood cells meet the corresponding antibodies in the serum, A versus A or B versus B, blood coagulation will occur immediately, which can lead to death in severe cases."

"The H gene can control the synthesis of H antigen. H is the antigen of Hh, the second largest blood group system. A and B are the antigens of the ABO blood group system. The two systems are inherited independently, but the H antigen is the precursor substance of the ABO blood group, with A,

The B antigenic sugar group needs to be connected to the H antigen before it can be converted into A and B antigens, showing the corresponding A, B, and AB phenotypes."

"If the expression of the H gene is missing in hematopoietic stem cells, there will be no H antigen in the blood, and A and B antigens will not be produced. This means that this blood can be transfused into any ABO blood type and is truly universal blood.

.”

"So, while inserting the active MLLT3 gene fragment, we also inhibited the expression of the H gene, so that the genetically modified hematopoietic stem cells can be induced to generate universal artificial blood that can be delivered to humans."

"Of course," he smiled: "Since there are hundreds of antigens on the human red blood cell membrane, some rare blood types are not included."

There was a burst of knowing chuckles from all around.

A young man in his early 20s said with excitement: "This is the legendary Bombay blood. This is a very rare blood type. I didn't expect that we could synthesize it in the laboratory. This is definitely a shocking breakthrough in synthetic biology."

.”

Everyone else nodded and praised him all the time.

"Bombay blood was discovered in Mumbai, India, in the 1950s. It is comparable to the legendary dinosaur blood in China. It seems that there are only more than a hundred cases in the country. It is of great significance!"

"This blood can be transfused to most people regardless of popular blood types. If used in large quantities, it can greatly improve the storage and transportation of blood banks."

"From now on, our country will never have a shortage of food. I feel so excited just thinking about it."

"This is the meaning of our work. To personally change the world, what job can compare with the sense of fulfillment?"

"Yeah, even if I keep working overtime during this period, it's still worth it."

"But we are only producing it in the laboratory, the real difficulty is yet to come."

"That's right." Ding Mian took over the conversation and said confidently: "In fact, many of the prerequisite theories for artificial blood are quite mature, and it is not particularly difficult to develop them in the laboratory."

"In the past few years, teams at home and abroad have been trying to generate hematopoietic stem cells outside the laboratory. Of course, some teams have made progress, but they only stay in the laboratory stage, and there is no further progress after animal experiments.

"

"We can go one step further and generate real artificial blood in the laboratory, which means we have gone further than others."

"However, there is still one last big boss on this difficult road, which is mass production."

"We are an enterprise. If the products we develop cannot be commercialized and mass-produced, it is meaningless."

Having said this, Ding Mian raised four fingers, and his slightly childish face finally turned serious.

"Let me summarize, there are five stages in the conversion of human epithelial cells into artificial blood."

“The first stage is the induction period, which is 0-8 days after the introduction of exogenous genes. During this period, epithelial cells will begin to be induced into iPS stem cells.

"The second stage, the differentiation period after this, about 7 to 10 days, is when the iPS stem cells transform into hematopoietic stem cells."

"The third stage involves genetic modification of hematopoietic stem cells, mainly MLLT3 and H genes. This technology is very mature and can be completed within 3 days.

"The fourth stage, about 15 days after cell fate determination, is the expansion period. At this time, the newly generated hematopoietic stem cells proliferate in large numbers and have transcriptomes and long-term self-renewal capabilities similar to normal adult hematopoietic stem cells. The length of this time

Depends on the number of hematopoietic stem cells required."

"In the fifth stage, three special combinations of factors are introduced again, and the hematopoietic stem cells are officially transformed into universal blood in the culture dish, which takes about a week."

"When the conversion is complete, we can collect the blood in the petri dish and store it for use."

"These five processes don't seem complicated, but if they are applied directly to biofactories without improvement, it may become a complete disaster during mass production."

"Next, our first priority is to do our best during the clinical trial period to improve the production process so that it can be successfully commercialized and mass-produced at an affordable cost."

"In this way, the artificial blood project can truly succeed, and our efforts over the past six months will be meaningful."

"Are you ready to overcome the next bigger difficulty?"

Ding Mian raised his clenched fists and shouted loudly.

"Ready!"

Everyone shouted in unison and roared.

Their eyes shot out with gleams of light, and their expressions were extremely excited, like a group of warriors getting ready to go to the battlefield.

Seeing everyone walking out of the laboratory in high spirits, Tang Que looked at Ding Mian and said with approval.

"What you just said was very good, and your mobilization skills are also good. You are as good as me."

Ding Mian chuckled and said, "Of course, I'm learning from you. Can the effect be bad?"

Tang Que smiled slightly and was about to say something modest.

But I heard Ding Mian continue: "Everyone in the biology laboratory has been conditioned by your PUA. I just learned how to turn it on and off, and the effect is naturally great."

He squeaked, snapped his fingers, and said triumphantly: "Brother Que, you are the boss. The effect of this brainwashing magic is really amazing. When I first saw it,

It was like a pupil earthquake. I never thought that the laboratory could be managed and played like this."

Tang Que's expression changed and turned as dark as the bottom of a pot.

A gleam flashed in his eyes, and he said calmly: "Okay, you can report it to General Wei later."

After saying that, he turned around and left.

"Ah, I was wrong, Brother Que, you shouldn't be so insignificant." Ding Mian suddenly panicked and hurriedly caught up.

"Mr. Wei is such a big shot. If you weren't there when I met him, I would be really nervous."

Tang Que touched his chin speechlessly, turned around and said, "You have been here for more than half a year, why are you still like this? You are not stable at all."

"Did you develop this artificial blood technology by yourself? If it hadn't been for the company's platform, if it hadn't been for the hard work of colleagues, and if it hadn't been for President Wei's presence, would you have achieved such results as soon as you entered the company?"

He shook his head and said, "You are raising your tail so quickly? When you can really develop something new, no matter how proud and complacent you are, I will not care about you, I will only cheer for you. Now."

, just save it."

"Originally, I wanted you to show your face in front of President Wei this time and gain impression points, forget it!"

"I'll do this report myself."

Ding Mian's face fell instantly, he pursed his lips and muttered in his heart before returning to his seat.

He is an only child with no brothers or sisters. Tang Que has always been with him when he was lonely since he was a child, so he subconsciously treats him as an elder brother. In a short period of time after starting work, he has not adapted to this hierarchical relationship between superiors and subordinates.

.

Therefore, after being scolded by Tang Que, he didn't feel any resistance. Instead, he knew that the other party's words were good words.

"Okay, isn't it just a matter of keeping a low profile and being insignificant? No one understands this better than me."

He turned on the computer, flicked his fingers, turned all his emotions into motivation, and devoted himself to selfless work.

****

Kunming First People's Hospital, Department of Hematology.

Early in the morning, Liu Zhengming walked to the office and saw someone waiting at the door.
To be continued...