#haematopoiesis

[bpod-bpod]

Blood to Brain

Bone marrow-derived (haematopoietic) stem cell transplants (HSCT), such as may be given for treating leukaemia, are being investigated as a means of delivering therapeutic proteins to the central nervous system. In this study, mice deficient in a protein called progranulin – mimicking the cause of neurological disease in humans – had levels restored by HSCT

Read the published research article here

Image from work by Pasqualina Colella and colleagues

Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA

Video originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Nature Communications, July 2024

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[popgenpapers]

Clonal dynamics and somatic evolution of haematopoiesis in mouse

http://dlvr.it/TDX50l

[leedsomics]

Single-cell multi-omics map of human foetal blood in Down's Syndrome

Down's Syndrome (DS) predisposes individuals to haematological abnormalities, such as increased number of erythrocytes and leukaemia in a process that is initiated before birth and is not entirely understood. To understand dysregulated hematopoiesis in DS, we integrated single-cell transcriptomics of over 1.1 million cells with chromatin accessibility and spatial transcriptomics datasets using human foetal liver and bone marrow samples from three disomic and 15 trisomic foetuses. We found that differences in gene expression in DS were both cell type- and environment-dependent. Furthermore, we found multiple lines of evidence that DS haematopoietic stem cells (HSCs) are "primed" to differentiate. We subsequently established a DS-specific map of enhancer-gene relationships in disomic and trisomic HSCs using 10X Multiome data. By integrating this map with genetic variants associated with blood cell variation, we discovered that trisomy restructured enhancer-gene maps to dysregulate enhancer activity and gene expression critical to erythroid lineage differentiation. Further, as DS mutations display a signature of oxidative stress, we validated both increased mitochondrial mass and oxidative stress in DS, and observed that these mutations preferentially fell into regulatory regions of expressed genes in HSCs. Altogether, our single-cell, multi-omic resource provides a high-resolution molecular map of foetal haematopoiesis in Down's Syndrome and indicates significant enhancer-gene restructuring giving rise to co-occurring haematological conditions. http://dlvr.it/SwgGVb

[snehasne872]

What Is Clonal Haematopoiesis, What To Know?

In the intricate landscape of the human body, the circulatory system, powered by blood, stands as a crucial lifeline. However, beneath the surface of this vital fluid lies a fascinating phenomenon known as clonal haematopoiesis. Recently discovered and still under extensive research, clonal haematopoiesis has piqued the curiosity of scientists and medical professionals alike. In this blog, we will delve into the world of clonal haematopoiesis, exploring its definition, implications, and what we need to know about this enigmatic process.

Understanding Clonal Haematopoiesis

Clonal hematopoiesis is a relatively new term in the realm of medicine, first gaining recognition in the early 2010s. It refers to a condition where a single mutated stem cell or a group of mutated stem cells give rise to identical copies of themselves, leading to the production of a large number of identical blood cells. These cells can carry specific genetic mutations that confer a competitive advantage to them, allowing them to outgrow and outnumber their normal counterparts in the blood.

Normally, the genetic material of our cells is susceptible to random mutations due to environmental factors or errors in DNA replication. However, our body has a robust system to repair these mutations and maintain the integrity of our genetic code. Clonal haematopoiesis arises when this repair mechanism fails, leading to the accumulation of mutations in a small population of blood stem cells.

Implications and Significance

While clonal haematopoiesis was initially considered a benign age-related phenomenon, recent research has revealed its potential connection to serious health conditions. Studies have shown that individuals with clonal haematopoiesis have a higher risk of developing various hematologic malignancies, such as leukemia, myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs). Additionally, it has been linked to an increased risk of cardiovascular diseases, including heart attacks and strokes.

The most common mutation observed in clonal haematopoiesis involves a gene called DNMT3A. Other frequently mutated genes include TET2, ASXL1, and JAK2. Interestingly, some of these mutations are shared with certain blood cancers, further highlighting the complexity of this phenomenon.

Diagnostic Challenges

Detecting clonal haematopoiesis poses a challenge in clinical settings. It is often asymptomatic, and its presence may go unnoticed without thorough genetic testing of blood samples. As such, researchers are working to develop more accurate and sensitive tests to identify individuals at risk.

Potential Therapeutic Avenues

Despite the potential risks associated with clonal haematopoiesis, researchers are optimistic about uncovering therapeutic avenues. By understanding the molecular and cellular mechanisms underlying this phenomenon, they hope to develop targeted treatments to prevent the progression of clonal haematopoiesis into full-blown blood disorders.

Moreover, ongoing research is focused on identifying factors that contribute to the development of clonal haematopoiesis. Genetic predisposition, lifestyle choices, and environmental factors are all areas of investigation.

Conclusion

Clonal hematopoiesis may still be a relatively new concept, but its implications for health and disease have caught the attention of the medical community. Understanding the mysteries of this phenomenon holds the potential to revolutionize the diagnosis and treatment of blood disorders and cardiovascular diseases. As research continues, we can hope for a future where early detection and intervention will minimize the impact of clonal hematopoiesis on our health, leading to improved outcomes and quality of life for affected individuals.

[ameerunsblog]

Pathophysiology Of Erythroid Disorders Notes

[nosotinylife]

Author Correction: Clonal haematopoiesis and risk of chronic liver disease

http://dlvr.it/Src1sm

[freedomainnames]

haematopoiesis-praxis.org

[tumimmtxpapers]

Clonal haematopoiesis and dysregulation of the immune system

Age-related diseases are frequently linked to pathological immune dysfunction, including excessive inflammation, autoreactivity and immunodeficiency. Recent analyses of human genetic data have revealed that somatic mutations and mosaic chromosomal alterations in blood cells - a condition known as clonal haematopoiesis (CH) - are associated with ageing and pathological immune dysfunction. Indeed, large-scale epidemiological studies and experimental mouse models have demonstrated that CH can... http://dlvr.it/SlFQq8

[meerschweinchen-archive]

what was so special about jesus i turn water into blood every day

[bpod-bpod]

Into Marrow’s World

Generation of human bone marrow organoids – complex 3D structures that mimic the haematopoietic [blood cell forming] microenvironment to enable study of blood and immune cell development, disorders and their treatments

Read the published research article here

Still from a video from work by Stephanie Frenz-Wiessner and colleagues

Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany

Video originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Nature Methods, February 2024

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[escapekit]

Haematopoiesis I LA-based artist RUBEN shares Hematopoiesis, the process of formation of blood cellular components, and therefore life.

This is the first release of a total of 280 images created during the last five months, 50 cells handcrafted one by one with paint, liquid thickener, ferrofluid and magnets, then photographed to create this collection.

[emmanuelm23]

Why the skeleton system so important?

The skeleton system has six major functions in our body.

Support -The skeleton provides the framework which supports the body and maintains its shape.

Movement- The joints between bones allow movement, some allowing a wider range of movement than others,

Protection-The skeleton helps to protect many vital internal organs from being damaged.

Blood cell production-The skeleton is the site of haematopoiesis, the development of blood cells that takes place in the bone marrow.

Storage-The bone matrix can store calcium and is involved in calcium metabolism, and bone marrow can store iron in ferritin and is involved in iron metabolism.

Endocrine regulation-Bone cells release a hormone called osteocalcin, which contributes to the regulation of blood sugar (glucose) and fat deposition.

[owlservice]

I went to the nurse for a blood test this morning. She forgot to release the tourniquet so the phials took a long time to fill up and my hand went numb. Cool though. Can't wait for my kidneys to notice the deficit and tell my bone marrow to undergo haematopoiesis to generate erythrocytes. Love the human body ... would love to have one some day ...

[hungryblueghost]

“I have taken a seat in Hades’ court. I  have eaten the pomegranate seeds. All 12. If I am to be trapped, I may as well be noble.” —Teo Mungaray, “Haematopoiesis”

[88y53]

Ultimate Fantastic Four biology

So, I've been reading a lot of Ultimate Fantastic Four recently, and I became fascinated by the hard-science approach the authors took to the lore. I won't say they did as much research into how the characters and how they should act, but that another story.

The authors had a rather brilliant take on the four's origins as an accident involving inter-universal teleportation instead of cosmic radiation: 

During the teleportation, their body's phase-space - every conceivable state could exist as - was randomized and changed into what they are now. I loved this new explanation, because no matter how improbable, they could come up with any arbitrary way to explain their powers. However, I noticed that after they gave a brief summation of Reed and Johnny's new bodies and how they functioned, they just kind of shrugged when it came to Ben and Sue (who literally admits has no idea how she can see when invisible). Which I think is kind of lazy. So, after a few hours of research, I came up with this list of theories over how their new bodies work.

Feel free to correct me if you spot mistakes.

Mr. Fantastic

Reed's new body is an infinitely extensible fluid-filled sack containing, in place of an alimentary canal and other organs, just a squishable bolus of microbes that perform all metabolic functions. His basic biology has more in common with Cephalopoda than mammals as he doesn't possess a centralized brain; his neurons (which measure in the 100 billion) are mainly found in nerve cords across is whole body, meaning that he has the largest brain-to-body mass ratio on earth. He has an extreme developed inner ear function that attach to specialized sac-like organs which can accurately sense the orientation of his body. This works in tandem with tension sensors in his limbs that help create a 3-d map of his body when stretched. His body also doesn't have any bones, but is supported by a system of inflatable bladders that mimic a skeletal structure. The only hard part of his entire body are his teeth, which are identical to human teeth. And while he does posses rudimentary lungs that he can use to respirate and speak, the bacterial stack inside his body that metabolize his food food are fully capable of taking in oxygen through his skin.

The Human Torch

Johnny's body creates high-efficiency plasma from his stores of body fat through a form of fusion, similar to that observed in mitochondria. This plasma is ejected through the seams of fire-resistant, microscopic, hexagonal scales and ignite on contact with air. The plasma has a high hydrogen content, and is surrounded by an exuded cloud of mono-atomic hydrogen atoms. The cloud provides him with sufficient positive buoyancy to float, and by forming a jet at his feet, he achieve a flight speed of 140 miles per hour, with his protective scales shielding him from the elements. He also has extremely developed sense of balance that aid him with maneuvering during flight, and his respiratory system is such that it allows him to function in low-oxygen environments such as high altitude, increased wind speed, and when his fire is activated.

The Invisible Woman

Sue's nervous system contain nodules that generate quantum mechanical interactions which assemble photonic molecules. Using radiation pressure, she creates transparent photonic lattices that are about a nanometer thick and produce a propellant force, and by phase-shifting the resonance of her photonic constructs, they provide a superluminal phase velocity of propagating waves. Such velocity preserves the original electromagnetic wave in front while waves curve past the intended area, thus becoming invisible. However, the field doesn't affect her eyes as they contain specialized lenses that can see and differentiate the field from open space like a sheet of glass. The nodules in her nervous system respond to the electrical currents generated when her neurons fire, so by going through physical mnemonics, she can send the required charge to the correct nodules for the desired effect. However, this process is very taxing as it requires a high-calorie intake to function.

The Thing

Ben's skin is a unique construction similar to deep-sea hydrothermal-vent snails, with three layers; the outer layer are tightly-packed scales mainly composed of granite, Quartz, potassium feldspar, biotite, plagioclase feldspar, and iron-mineralized sclerites, the middle layer is a flexible organic periostracum, and the innermost layer is made of aragonite. This armor doesn't contain nerve endings, and doesn't produce tactile sensation. Standing at 7 feet tall, his muscle fibers are analogous to tightly-packed steel cables, with leather-like tendons, and incredibly dense bone structure. His skull contains a thick layer of fluid around his brain that protects it from sudden impacts, and his eyes (which are sunken in and protected by a pronounced brow) have a transparent third eyelid that closes during a flight/flight response. His eyes compensate for this protection by being tube-shaped and containing more rods than their human counterpart, and a reflective surface behind his retinas. Allowing for incredible night-vision, enhanced peripheral visions and the ability to shift focus to essentially zoom in on a target.  His respiratory system doesn't posses a pleural cavity; rather his ample lungs are attached directly to his chest cavity and diaphragm. Using collagen fibers arranged in a loose formation that connect them to the chest walls, there is no constricting effect on the lungs, which are rich in capillaries to allow for ample blood supply and pleural fluid.  The most fascinating aspect of his biology are the colonies of endosymbiotic bacteria that aid in most of his metabolic functions; the bacteria that reside in his lungs utilize chemosynthesis which allows him to respirate in highly toxic environments with no ill effect. His digestive tract houses an extremely corrosive form of sulphuric acid which is contained by a stomach lining that also contains endosymbiotic bacteria, allowing him to basically consume any material, with jaws that are strong enough to break up rock and teeth that are rootless, so they must constantly be worn down. This process takes in necessary minerals which replenish any lost crust. Much of his body mass is concentrated in his torso and legs, which have cancellous bone in place of medullary cavities, thus strengthening the bones while still allowing haematopoiesis. The leg bones are structured on top of each other, to help distribute weight, and his large feet are flat with no arch that are lined with soft tissue that act as cushion pads. In walking, the legs act more like pendulums, that require his hips and shoulders to move laterally to create momentum. Due to the amount of stress placed on his joints, his body produces an extremely viscous fluid that reduces friction and shock during movement, which is fortunate because his steps measure on the Richter scale. The fluid is an ultrafiltrate from plasma, and contains proteins derived from the blood plasma and proteins that are produced by cells within the joint tissue. His hands lack a fifth digit, with the remaining four being very thick, lacking nails, and not very dexterous. Each digit has roughly 2-3 bones that are separated by enlarged hinge joints which are too densely packed to allow for a precision grip, though the thumb is still technically opposable.

[Author's Note: I had a section where I speculated on Ben and Reed's new reproductive systems, but I think I'll spare you of that.]