𝗦𝘁𝗲𝗺 𝗖𝗲𝗹𝗹𝘀: 𝗧𝗵𝗲 𝗢𝗿𝗶𝗴𝗶𝗻 
Hematopoietic stem cells (HSCs) reside in the bone marrow and possess the ability to self-renew and differentiate into all blood cell types [1]. 

HSCs share a common developmental origin with endothelial cells via 𝙝𝙚𝙢𝙖𝙣𝙜𝙞𝙤𝙗𝙡𝙖𝙨𝙩𝘴, 𝘭𝘪𝘯𝘬𝘪𝘯𝘨 𝘩𝘦𝘮𝘢𝘵𝘰𝘱𝘰𝘪𝘦𝘴𝘪𝘴 𝘵𝘰 𝘵𝘩𝘦 𝘤𝘢𝘳𝘥𝘪𝘰𝘷𝘢𝘴𝘤𝘶𝘭𝘢𝘳 𝘴𝘺𝘴𝘵𝘦𝘮 [1,2]. 

𝗣𝗿𝗼𝗴𝗲𝗻𝗶𝘁𝗼𝗿𝘀: 𝗕𝗿𝗮𝗻𝗰𝗵𝗶𝗻𝗴 𝗜𝗻𝘁𝗼 𝗟𝗶𝗻𝗲𝗮𝗴𝗲𝘀 
𝘊𝘰𝘮𝘮𝘰𝘯 𝘔𝘺𝘦𝘭𝘰𝘪𝘥 𝘗𝘳𝘰𝘨𝘦𝘯𝘪𝘵𝘰𝘳𝘴 (𝘊𝘔𝘗𝘴)→ neutrophils, monocytes/macrophages, dendritic cells, basophils, eosinophils, platelets. 
𝘊𝘰𝘮𝘮𝘰𝘯 𝘓𝘺𝘮𝘱𝘩𝘰𝘪𝘥 𝘗𝘳𝘰𝘨𝘦𝘯𝘪𝘵𝘰𝘳𝘴 (𝘊𝘓𝘗𝘴) → T cells, B cells, NK cells, innate-like lymphocytes [2]. 

𝗟𝗶𝗻𝗲𝗮𝗴𝗲 𝗧𝗿𝗲𝗲 𝗠𝗲𝘁𝗮𝗽𝗵𝗼𝗿 
Imagine a tree: the roots are HSCs, the trunk represents progenitor differentiation, and the branches are mature immune cells spreading into tissues and circulation. 𝘛𝘩𝘦 𝘤𝘢𝘳𝘥𝘪𝘰𝘷𝘢𝘴𝘤𝘶𝘭𝘢𝘳 𝘴𝘺𝘴𝘵𝘦𝘮 𝘢𝘤𝘵𝘴 𝘭𝘪𝘬𝘦 𝘵𝘩𝘦 𝘪𝘳𝘳𝘪𝘨𝘢𝘵𝘪𝘰𝘯 𝘯𝘦𝘵𝘸𝘰𝘳𝘬, transporting branches throughout the body. 

𝗦𝘁𝘂𝗱𝘆𝗶𝗻𝗴 𝗛𝗲𝗺𝗮𝘁𝗼𝗽𝗼𝗶𝗲𝘀𝗶𝘀 𝗶𝗻 𝘁𝗵𝗲 𝗟𝗮𝗯 
𝘌𝘹 𝘷𝘪𝘷𝘰 HSC/progenitor cultures allow observation of differentiation. 
Techniques like 𝘧𝘭𝘰𝘸 𝘤𝘺𝘵𝘰𝘮𝘦𝘵𝘳𝘺, 𝘴𝘪𝘯𝘨𝘭𝘦-𝘤𝘦𝘭𝘭 𝘙𝘕𝘈 𝘴𝘦𝘲𝘶𝘦𝘯𝘤𝘪𝘯𝘨, 𝘢𝘯𝘥 𝘤𝘰𝘭𝘰𝘯𝘺-𝘧𝘰𝘳𝘮𝘪𝘯𝘨 𝘢𝘴𝘴𝘢𝘺𝘴 reveal lineage and functional states. 
𝘔𝘰𝘶𝘴𝘦 𝘮𝘰𝘥𝘦𝘭𝘴 𝘢𝘯𝘥 𝘩𝘶𝘮𝘢𝘯𝘪𝘻𝘦𝘥 𝘴𝘺𝘴𝘵𝘦𝘮𝘴 track hematopoietic cell migration and function in vivo [1,3].   

𝗖𝗼𝗻𝗻𝗲𝗰𝘁𝗶𝗼𝗻 𝘁𝗼 𝗜𝗺𝗺𝘂𝗻𝗼𝘀𝗲𝗻𝗲𝘀𝗰𝗲𝗻𝗰𝗲 
HSCs gradually lose selfrenewal capacity and show lineage bias toward myeloid cells, reducing production of naïve lymphocytes [4]. This contributes to immunosenescence, weaker adaptive responses, and chronic low-grade inflammation (´𝗶𝗻𝗳𝗹𝗮𝗺𝗺𝗮𝗴𝗶𝗻𝗴´). 
𝘛𝘩𝘦 𝘚𝘤𝘩𝘪𝘳𝘮𝘣𝘦𝘤𝘬 𝘵𝘦𝘢𝘮 𝘢𝘵 𝘜𝘭𝘮 investigates these mechanisms, showing how aged HSCs drive immune remodeling across the lifespan[4]. 

𝗧𝗮𝗸𝗲𝗮𝘄𝗮𝘆 
Hematopoiesis is the 𝗳𝗼𝘂𝗻𝗱𝗮𝘁𝗶𝗼𝗻 𝗼𝗳 𝗶𝗺𝗺𝘂𝗻𝗶𝘁𝘆, 𝗰𝗼𝗻𝗻𝗲𝗰𝘁𝗲𝗱 𝘁𝗼 𝘁𝗵𝗲 𝗰𝗮𝗿𝗱𝗶𝗼𝘃𝗮𝘀𝗰𝘂𝗹𝗮𝗿 𝘀𝘆𝘀𝘁𝗲𝗺, and measurable in experimental systems. 

𝗣𝗮𝗿𝗮𝗱𝗼𝘅𝗶𝗰𝗮𝗹 𝗤𝘂𝗲𝘀𝘁𝗶𝗼𝗻 
If all immune cells originate from a single stem cell, why do healthy individuals show dramatic differences in immune cell composition? 

Stay tuned for 𝗗𝗮𝘆 𝟱: 𝗪𝗵𝗮𝘁 𝗮𝗿𝗲 𝗰𝘆𝘁𝗼𝗸𝗶𝗻𝗲𝘀? 

𝗥𝗲𝗳𝗲𝗿𝗲𝗻𝗰𝗲𝘀 
 1. DOI: 10.1016/j.cell.2008.01.025 
 2. DOI: 10.1016/j.stem.2012.01.006 
 3. DOI: 10.1038/nature12984 
 4. doi: 10.1182/blood-2018-02-831065 

  

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