10/19
Control of cell state transitions (Nature 2022 Boris N. Kholodenko)
The researchers constructed the cSTAR model (Cell state transition assessment and regulation) to distinguish cell states, quantify decision elements, reconstruct the network of mechanisms that control cell state transitions, and identify allowable manipulation of cell state transitions.
Cell states are switchable. However, understanding of how cellular networks drive cell state transitions and how cell states are purposefully manipulated and controlled is lacking
cSTAR model: is used to differentiate cellular states, quantify their determinants, reconstruct the network of mechanisms that control cellular state transitions, and identify changes in cellular states that can be identified
The construction of cSTAR needs
Control of cell state transitions (Nature 2022 Boris N. Kholodenko)
The researchers constructed the cSTAR model (Cell state transition assessment and regulation) to distinguish cell states, quantify decision elements, reconstruct the network of mechanisms that control cell state transitions, and identify allowable manipulation of cell state transitions.
Cell states are switchable. However, understanding of how cellular networks drive cell state transitions and how cell states are purposefully manipulated and controlled is lacking
cSTAR model: is used to differentiate cellular states, quantify their determinants, reconstruct the network of mechanisms that control cellular state transitions, and identify changes in cellular states that can be identified
The construction of cSTAR needs
Efficiently separate data by clustering the data and constructing a "hyperplane that separates molecular features of cell states, maximizing the distance between data points belonging to different cell states"
Construct a state transition vector representing a path from one cell state center to another cell state center in molecular data space
Dynamic phenotypic characterization, quantifying phenotypic changes in cells in response to perturbation by measuring whether the perturbation shifts the state center toward or away from the hyperplane
Bayesian formulation for modular response analysis, reconstructing the topology, direction, and strength of causal connections between core network nodes created by components specified by state transition vectors
Computational mechanical models based on ordinary differential equations or stochastic differential equations
Construct a state transition vector representing a path from one cell state center to another cell state center in molecular data space
Dynamic phenotypic characterization, quantifying phenotypic changes in cells in response to perturbation by measuring whether the perturbation shifts the state center toward or away from the hyperplane
Bayesian formulation for modular response analysis, reconstructing the topology, direction, and strength of causal connections between core network nodes created by components specified by state transition vectors
Computational mechanical models based on ordinary differential equations or stochastic differential equations
10/19
Maturation and circuit integration of transplanted human cortical organoids (Nature 2022 Sergiu P. Pașca Stanford)
Transplantation of human cortical organoids (hCO) into the rat brain allowed normal development, with neurons maturing and participating in circuit integration to control behavior.
This approach may be useful for clinical detection of circuit phenotypes in patient-derived cells.
Maturation and circuit integration of transplanted human cortical organoids (Nature 2022 Sergiu P. Pașca Stanford)
Transplantation of human cortical organoids (hCO) into the rat brain allowed normal development, with neurons maturing and participating in circuit integration to control behavior.
This approach may be useful for clinical detection of circuit phenotypes in patient-derived cells.
10/24
Mammalian oocytes store mRNAs in a mitochondria-associated membraneless compartment (Science 2022 MPI Melina Schuh)
Mammalian oocytes stop transcription during later stages of growth and do not turn it back on until the embryonic genome is activated after fertilization - Thus, oocyte development into a mature egg occurs without transcription.
During this process, the oocyte must rely on previously stored mRNA to translate the new protein
Previous studies have identified various types of mRNA-storing membraneless compartments in non-mammalian oocytes. However, it is unclear where and how mRNA is stored in mammalian oocytes.
This paper finds that mammalian oocytes store mRNA in a mitochondria-associated membraneless compartment
The researchers identified RNA-binding proteins highly expressed in the cytoplasm of mouse oocytes by mass spectrometry and analyzed the localization of these proteins by immunostaining. These proteins were found to aggregate near mitochondria and form clusters with mitochondria.
In contrast, these RNA-binding proteins did not co-localize with other organelles, or only partially co-localized. RNA in situ hybridization (RNA-FISH) experiments revealed that mRNA was also localized in this structure, suggesting that it is an mRNA reservoir. Because this structure is significantly different from previously discovered RNA storage compartments, the researchers named the structure the mitochondria-associated ribonucleoprotein domain, or MARDO for short.
Mammalian oocytes store mRNAs in a mitochondria-associated membraneless compartment (Science 2022 MPI Melina Schuh)
Mammalian oocytes stop transcription during later stages of growth and do not turn it back on until the embryonic genome is activated after fertilization - Thus, oocyte development into a mature egg occurs without transcription.
During this process, the oocyte must rely on previously stored mRNA to translate the new protein
Previous studies have identified various types of mRNA-storing membraneless compartments in non-mammalian oocytes. However, it is unclear where and how mRNA is stored in mammalian oocytes.
This paper finds that mammalian oocytes store mRNA in a mitochondria-associated membraneless compartment
The researchers identified RNA-binding proteins highly expressed in the cytoplasm of mouse oocytes by mass spectrometry and analyzed the localization of these proteins by immunostaining. These proteins were found to aggregate near mitochondria and form clusters with mitochondria.
In contrast, these RNA-binding proteins did not co-localize with other organelles, or only partially co-localized. RNA in situ hybridization (RNA-FISH) experiments revealed that mRNA was also localized in this structure, suggesting that it is an mRNA reservoir. Because this structure is significantly different from previously discovered RNA storage compartments, the researchers named the structure the mitochondria-associated ribonucleoprotein domain, or MARDO for short.
10/24
Differential mosquito attraction to humans is associated with skin-derived carboxylic acid levels (2022 Cell Rockefeller University Leslie B. Vosshall)
The paper found that some people are more attractive to mosquitoes due to different skin odors.
These people have higher levels of carboxylic acids on their skin, and mosquitoes with deficient sense of smell will show a decrease in preference, but they still can distinguish people with highly attracted odor and non-attractive odor.
Differential mosquito attraction to humans is associated with skin-derived carboxylic acid levels (2022 Cell Rockefeller University Leslie B. Vosshall)
The paper found that some people are more attractive to mosquitoes due to different skin odors.
These people have higher levels of carboxylic acids on their skin, and mosquitoes with deficient sense of smell will show a decrease in preference, but they still can distinguish people with highly attracted odor and non-attractive odor.
10/24
An evolutionary trade-off between host immunity and metabolism drives fatty liver in male mice (2022 Science Holly A. Ingraham Ajay Chawla)
Compared with premenopausal women, men are more likely to suffer from abnormal accumulation of liver fat, non-alcoholic fatty liver disease, liver fibrosis and liver tumors
Sex differences in hepatic gene expression are regulated by transient secretion patterns of pituitary growth hormone
BCL6 is a class of sex-dependent, growth hormone-regulated hepatocyte transcription factors.
The paper found that BCL6 played a role in promoting the phenotype that male mice are more susceptible to high-fat diet-induced nonalcoholic fatty liver disease
In the case of bacterial infection, BCL6 can increase male survival rate, which is an evolutionary trade-off.
An evolutionary trade-off between host immunity and metabolism drives fatty liver in male mice (2022 Science Holly A. Ingraham Ajay Chawla)
Compared with premenopausal women, men are more likely to suffer from abnormal accumulation of liver fat, non-alcoholic fatty liver disease, liver fibrosis and liver tumors
Sex differences in hepatic gene expression are regulated by transient secretion patterns of pituitary growth hormone
BCL6 is a class of sex-dependent, growth hormone-regulated hepatocyte transcription factors.
The paper found that BCL6 played a role in promoting the phenotype that male mice are more susceptible to high-fat diet-induced nonalcoholic fatty liver disease
In the case of bacterial infection, BCL6 can increase male survival rate, which is an evolutionary trade-off.
10/25
Tissue-specific Grb10/Ddc insulator drives allelic architecture for cardiac development (2022 Molecular Cell Upenn Marisa S. Bartolomei)
Diploid organisms have two sets of chromosomes, one from each parent.
In mammals, there are about 200 genes called imprinted genes that express genes from only one parent. These imprinted genes in the germline carry DNA methylation memory from the parent.
These imprinted genes in the germline carry DNA methylation memories from their parents.
DNA methylation-marked regions are also known as imprinting control regions (ICRs)
In addition to being a marker of parental memory, ICRs also control the expression of imprinted genes by coordinating, for example, noncoding RNAs and enhancers.
This paper identifies an unconventional differentially methylated region (DMRs) as a specific mechanism by which Grb10 and Ddc imprinted gene insulators regulate cardiac and muscle development.
Tissue-specific Grb10/Ddc insulator drives allelic architecture for cardiac development (2022 Molecular Cell Upenn Marisa S. Bartolomei)
Diploid organisms have two sets of chromosomes, one from each parent.
In mammals, there are about 200 genes called imprinted genes that express genes from only one parent. These imprinted genes in the germline carry DNA methylation memory from the parent.
These imprinted genes in the germline carry DNA methylation memories from their parents.
DNA methylation-marked regions are also known as imprinting control regions (ICRs)
In addition to being a marker of parental memory, ICRs also control the expression of imprinted genes by coordinating, for example, noncoding RNAs and enhancers.
This paper identifies an unconventional differentially methylated region (DMRs) as a specific mechanism by which Grb10 and Ddc imprinted gene insulators regulate cardiac and muscle development.
10/26
Time-restricted feeding mitigates obesity through adipocyte thermogenesis (2022 Science Joseph Bass Northwest University)
Excessive consumption of food is also associated with disturbances in the meal timing and metabolic cycle of one's own biological clock, that is, eating at inappropriate times is more likely to lead to fat accumulation.
Genetically induced disruption of the circadian clock can cause nocturnal animals to consume more food in the day time (dormancy period) and produce more severe obesity problems
Eating at the wrong time worsens food-induced obesity. But limiting high-calorie food to periods of activity can improve metabolism and support health.
This paper reports that the circadian rhythm negatively regulates the transcription factor, ZFP423, through thermogenesis. ZFP423 regulates creatine content in adipose tissue, and creatine content promotes ineffective creatine cycle to further regulate thermogenesis; ultimately regulates energy metabolism under a high-fat diet.
Time-restricted feeding mitigates obesity through adipocyte thermogenesis (2022 Science Joseph Bass Northwest University)
Excessive consumption of food is also associated with disturbances in the meal timing and metabolic cycle of one's own biological clock, that is, eating at inappropriate times is more likely to lead to fat accumulation.
Genetically induced disruption of the circadian clock can cause nocturnal animals to consume more food in the day time (dormancy period) and produce more severe obesity problems
Eating at the wrong time worsens food-induced obesity. But limiting high-calorie food to periods of activity can improve metabolism and support health.
This paper reports that the circadian rhythm negatively regulates the transcription factor, ZFP423, through thermogenesis. ZFP423 regulates creatine content in adipose tissue, and creatine content promotes ineffective creatine cycle to further regulate thermogenesis; ultimately regulates energy metabolism under a high-fat diet.
10/27
CRISPR/Cas9-induced structural variations expand in T lymphocytes in vivo (2022 Nucleic Acids Research 胡家志/徐墨 Peking/Tsinghua)
CRISPR-Cas gene editing tools are widely used in scientific research and clinical practice. However, in addition to on-target products and off-target editing, CRISPR-Cas also produces chromosomal structural variations (SVs) such as chromosomal translocations and large deletions, as well as massive viral DNA insertion
This paper uses the high-throughput sequencing method PEM-seq (primer-extension-mediated sequencing) to sensitively track chromosomal structural abnormalities and the fate of viral DNA insertions in CRISPR-Cas9 edited T cells after infusion into mice.
Among 16 mice infused with edited T-cells, two of them were found with significant expansion of T-cell monoclonals.
CRISPR/Cas9-induced structural variations expand in T lymphocytes in vivo (2022 Nucleic Acids Research 胡家志/徐墨 Peking/Tsinghua)
CRISPR-Cas gene editing tools are widely used in scientific research and clinical practice. However, in addition to on-target products and off-target editing, CRISPR-Cas also produces chromosomal structural variations (SVs) such as chromosomal translocations and large deletions, as well as massive viral DNA insertion
This paper uses the high-throughput sequencing method PEM-seq (primer-extension-mediated sequencing) to sensitively track chromosomal structural abnormalities and the fate of viral DNA insertions in CRISPR-Cas9 edited T cells after infusion into mice.
Among 16 mice infused with edited T-cells, two of them were found with significant expansion of T-cell monoclonals.
11/1
Substrate-driven assembly of a translocon for multipass membrane proteins (Nature 2022 Robert J. Keenan University of Chicago)
Mechanism of an intramembrane chaperone for multipass membrane proteins (Nature 2022 MRC Ramanujan S. Hegde)
Most membrane proteins are synthesized on the rough endoplasmic reticulum, ribosomes are docked on the translocon, and the nascent peptide chain in the scope of the heterogeneity factor complex
The endoplasmic reticulum multi-channel translocon is a dynamic assemblage, and its different subunit compositions can be adjusted with the co-translational process to suit the needs of different substrate biosynthesis.
Substrate-driven assembly of a translocon for multipass membrane proteins (Nature 2022 Robert J. Keenan University of Chicago)
Mechanism of an intramembrane chaperone for multipass membrane proteins (Nature 2022 MRC Ramanujan S. Hegde)
Most membrane proteins are synthesized on the rough endoplasmic reticulum, ribosomes are docked on the translocon, and the nascent peptide chain in the scope of the heterogeneity factor complex
The endoplasmic reticulum multi-channel translocon is a dynamic assemblage, and its different subunit compositions can be adjusted with the co-translational process to suit the needs of different substrate biosynthesis.
11/1
Ancient homomorphy of molluscan sex chromosomes sustained by reversible sex-biased genes and sex determiner translocation (Nature Ecology & Evolution 2022 中国海洋大学)
Traditional evolution review believe that sex chromosomes originate from autosomes, and the emergence of sex-determining genes will cause recombination inhibition between sex chromosomes and gradually degenerate to form heteromorphic sex chromosomes
Heteromorphic sex chromosomes are considered to be the "final fate" of the sex chromosome evolutionary pathway. However, contrary to this prediction, more and more evidences show that there are species with homomorphic sex chromosomes (two sex chromosomes without obvious differentiation) in the animal kingdom. According to statistics, about 90% of shellfish, fish and 96 The sex chromosomes of % of reptiles are not differentiated.
Ancient homomorphy of molluscan sex chromosomes sustained by reversible sex-biased genes and sex determiner translocation (Nature Ecology & Evolution 2022 中国海洋大学)
Traditional evolution review believe that sex chromosomes originate from autosomes, and the emergence of sex-determining genes will cause recombination inhibition between sex chromosomes and gradually degenerate to form heteromorphic sex chromosomes
Heteromorphic sex chromosomes are considered to be the "final fate" of the sex chromosome evolutionary pathway. However, contrary to this prediction, more and more evidences show that there are species with homomorphic sex chromosomes (two sex chromosomes without obvious differentiation) in the animal kingdom. According to statistics, about 90% of shellfish, fish and 96 The sex chromosomes of % of reptiles are not differentiated.
Paper/Seminar Record
11/1 Ancient homomorphy of molluscan sex chromosomes sustained by reversible sex-biased genes and sex determiner translocation (Nature Ecology & Evolution 2022 中国海洋大学) Traditional evolution review believe that sex chromosomes originate from autosomes, and…
This paper reveals that the maintenance of homomorphic sex chromosomes is the "regular" of sex chromosome evolution, and the differentiation of heteromorphic sex chromosomes requires additional evolutionary power, which is a branch of the entire evolutionary pathway rather than "final destiny".
Microtubule nucleation: beyond the template
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621832/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621832/
PubMed Central (PMC)
Tissue patterning and cellular mechanics
In development, cells organize into biological tissues through cell growth, migration, and differentiation. Globally, this process is dictated by a genetically encoded program in which secreted morphogens and cell–cell interactions prompt the ...
11/1
Importin α Partitioning to the Plasma Membrane Regulates Intracellular Scaling (Cell 2019 Rebecca Heald UCB)
importin α: a conserved surface area-to-volume sensor that scales intracellular structures to cell size / a highly conserved and abundant nuclear transport factor that binds nuclear localization sequence (NLS)-containing proteins
palmitoylation-dependent importin α membrane association regulates mitotic spindle and nuclear scaling during Xenopus embryogenesis by providing a measure of the cell surface area-to-volume ratio
One technique - PEGylated surfactant
adding 2 μL of the extract reaction mixture on ice to 50 μL of the appropriate surfactant/lipid mixture
Cithrol DPHS resuspended in squalene at 50 mg/mL served as the surfactant to form inert membrane droplets, while total bovine liver extracts (preparation detailed above) were used as the physiological membrane surfactant
The extract/surfactant mixture was then pipetted up and down with a 20 μL pipette tip set to maximum volume approximately 10-20 times, depending on the desired size range of droplets desired.
The emulsified mixture was then added to a custom-built chamber composed of vacuum grease (Dow Corning) on a coverslip
Importin α Partitioning to the Plasma Membrane Regulates Intracellular Scaling (Cell 2019 Rebecca Heald UCB)
importin α: a conserved surface area-to-volume sensor that scales intracellular structures to cell size / a highly conserved and abundant nuclear transport factor that binds nuclear localization sequence (NLS)-containing proteins
palmitoylation-dependent importin α membrane association regulates mitotic spindle and nuclear scaling during Xenopus embryogenesis by providing a measure of the cell surface area-to-volume ratio
One technique - PEGylated surfactant
adding 2 μL of the extract reaction mixture on ice to 50 μL of the appropriate surfactant/lipid mixture
Cithrol DPHS resuspended in squalene at 50 mg/mL served as the surfactant to form inert membrane droplets, while total bovine liver extracts (preparation detailed above) were used as the physiological membrane surfactant
The extract/surfactant mixture was then pipetted up and down with a 20 μL pipette tip set to maximum volume approximately 10-20 times, depending on the desired size range of droplets desired.
The emulsified mixture was then added to a custom-built chamber composed of vacuum grease (Dow Corning) on a coverslip
11/2
Phenotypic plasticity and genetic control in colorectal cancer evolution (Nature 2022 British Andrea Sottoriva & Trevor A. Graham)
The article found a common phenomenon in CRC tumors (colorectal cancer), that tumors can acquire phenotypic plasticity without genetic factors (epigenetic or genetic) changes.
Phenotypic plasticity and genetic control in colorectal cancer evolution (Nature 2022 British Andrea Sottoriva & Trevor A. Graham)
The article found a common phenomenon in CRC tumors (colorectal cancer), that tumors can acquire phenotypic plasticity without genetic factors (epigenetic or genetic) changes.
11/2
The gut-to-brain axis for toxin-induced defensive responses (Cell 2022 北京生命科学研究所 曹鹏)
After food poisoning, the brain initiates a series of defense responses such as nausea and vomiting. Through vomiting, the human body excretes the ingested toxic food out of the digestive tract, preventing the pathogen from further invading the body.
Through the disgusting emotion of nausea, the brain can form a long-term memory of the characteristics of a poisonous food, so as to avoid eating the poisonous food again in the future.
Studying the "nausea-vomiting" response is difficult because rodents commonly used in the laboratory, such as mice and rats, do not exhibit vomiting behavior. Rodents are unable to spit food out of their stomachs, thought to be due to underdeveloped smooth muscles in the digestive tract
Past research has only been able to use animals that exhibit vomiting behavior, such as dogs and ferrets. They found that cutting the subphrenic vagus nerve can effectively block the vomiting response, indicating that vomiting depends on the "gut-to-brain" axis between the gastrointestinal tract and the brain.
Brain regions involved in the vomiting response identified by means of damage and electrical stimulation
Through pharmacological methods, it was found that antagonists of 5-HT3R and NK1R can effectively inhibit the emesis response
To elucidate the mechanism by which the brain initiates the "nausea-vomiting" response, in addition to appropriate animal models and research paradigms, three long-standing mysteries need to be solved.
First, after the gastrointestinal tract was invaded by pathogens, which type of intestinal cells gave this important information to the vagus nerve?
Second, what is the identity and characteristics of the sensory neurons in the vagus nerve responsible for interfacing with the gut "intelligence"?
Third, when the brain receives the information of pathogen invasion from the vagus nerve, how does it quickly and synchronously initiate a series of defense responses such as nausea and vomiting?
This study established a new paradigm for studying the "nausea-vomiting" response using mice as an animal model, and initially revealed the molecular, cellular and neural circuit mechanisms that trigger the "nausea-vomiting" response by the brain's perception of pathogen invasion.
The gut-to-brain axis for toxin-induced defensive responses (Cell 2022 北京生命科学研究所 曹鹏)
After food poisoning, the brain initiates a series of defense responses such as nausea and vomiting. Through vomiting, the human body excretes the ingested toxic food out of the digestive tract, preventing the pathogen from further invading the body.
Through the disgusting emotion of nausea, the brain can form a long-term memory of the characteristics of a poisonous food, so as to avoid eating the poisonous food again in the future.
Studying the "nausea-vomiting" response is difficult because rodents commonly used in the laboratory, such as mice and rats, do not exhibit vomiting behavior. Rodents are unable to spit food out of their stomachs, thought to be due to underdeveloped smooth muscles in the digestive tract
Past research has only been able to use animals that exhibit vomiting behavior, such as dogs and ferrets. They found that cutting the subphrenic vagus nerve can effectively block the vomiting response, indicating that vomiting depends on the "gut-to-brain" axis between the gastrointestinal tract and the brain.
Brain regions involved in the vomiting response identified by means of damage and electrical stimulation
Through pharmacological methods, it was found that antagonists of 5-HT3R and NK1R can effectively inhibit the emesis response
To elucidate the mechanism by which the brain initiates the "nausea-vomiting" response, in addition to appropriate animal models and research paradigms, three long-standing mysteries need to be solved.
First, after the gastrointestinal tract was invaded by pathogens, which type of intestinal cells gave this important information to the vagus nerve?
Second, what is the identity and characteristics of the sensory neurons in the vagus nerve responsible for interfacing with the gut "intelligence"?
Third, when the brain receives the information of pathogen invasion from the vagus nerve, how does it quickly and synchronously initiate a series of defense responses such as nausea and vomiting?
This study established a new paradigm for studying the "nausea-vomiting" response using mice as an animal model, and initially revealed the molecular, cellular and neural circuit mechanisms that trigger the "nausea-vomiting" response by the brain's perception of pathogen invasion.
chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.pnas.org/doi/pdf/10.1073/pnas.2121147119
11/4
Emergent properties of mitotic chromosomes (Current Opinion in Cell Biology 2020 Rebecca Heald UCB)
How to connect the molecular-level activities to large-scale changes in whole-chromosome architecture that determine mitotic chromosome size, shape, and function.
In conclusion, multiple biochemical activities at the molecular level come together to mediate the large-scale chromosome organization and dynamics observed during mitosis.
Two major challenges:
integrating the many sources of structural information (imaging, sequencing, biochemistry) into a comprehensive, multiscale model for mitotic chromosome architecture
relating the structure and mechanics of mitotic chromosomes to their functions in cell division and epigenetic inheritance.
Emergent properties of mitotic chromosomes (Current Opinion in Cell Biology 2020 Rebecca Heald UCB)
How to connect the molecular-level activities to large-scale changes in whole-chromosome architecture that determine mitotic chromosome size, shape, and function.
In conclusion, multiple biochemical activities at the molecular level come together to mediate the large-scale chromosome organization and dynamics observed during mitosis.
Two major challenges:
integrating the many sources of structural information (imaging, sequencing, biochemistry) into a comprehensive, multiscale model for mitotic chromosome architecture
relating the structure and mechanics of mitotic chromosomes to their functions in cell division and epigenetic inheritance.