Alternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cells
Rare multipotent stem cells replenish millions of blood cells per second through a time-consuming process, passing through multiple stages of increasingly lineage-restricted progenitors. Although insults to the blood-forming system highlight the need for more rapid blood replenishment from stem cell...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Nature Research
2024
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| _version_ | 1811139550371643392 |
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| author | Carrelha, J Mazzi, S Winroth, A Hagemann-Jensen, M Ziegenhain, C Högstrand, K Seki, M Brennan, MS Lehander, M Wu, B Meng, Y Markljung, E Norfo, R Ishida, H Belander Strålin, K Grasso, F Simoglou Karali, C Aliouat, A Hillen, A Chari, E Siletti, K Thongjuea, S Mead, AJ Linnarsson, S Nerlov, C Jacobsen, SEW |
| author_facet | Carrelha, J Mazzi, S Winroth, A Hagemann-Jensen, M Ziegenhain, C Högstrand, K Seki, M Brennan, MS Lehander, M Wu, B Meng, Y Markljung, E Norfo, R Ishida, H Belander Strålin, K Grasso, F Simoglou Karali, C Aliouat, A Hillen, A Chari, E Siletti, K Thongjuea, S Mead, AJ Linnarsson, S Nerlov, C Jacobsen, SEW |
| author_sort | Carrelha, J |
| collection | OXFORD |
| description | Rare multipotent stem cells replenish millions of blood cells per second through a time-consuming process, passing through multiple stages of increasingly lineage-restricted progenitors. Although insults to the blood-forming system highlight the need for more rapid blood replenishment from stem cells, established models of hematopoiesis implicate only one mandatory differentiation pathway for each blood cell lineage. Here, we establish a nonhierarchical relationship between distinct stem cells that replenish all blood cell lineages and stem cells that replenish almost exclusively platelets, a lineage essential for hemostasis and with important roles in both the innate and adaptive immune systems. These distinct stem cells use cellularly, molecularly and functionally separate pathways for the replenishment of molecularly distinct megakaryocyte-restricted progenitors: a slower steady-state multipotent pathway and a fast-track emergency-activated platelet-restricted pathway. These findings provide a framework for enhancing platelet replenishment in settings in which slow recovery of platelets remains a major clinical challenge. |
| first_indexed | 2024-09-25T04:07:52Z |
| format | Journal article |
| id | oxford-uuid:c7f4abf8-2f57-4c09-9ff6-037b4bf28911 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:07:52Z |
| publishDate | 2024 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:c7f4abf8-2f57-4c09-9ff6-037b4bf289112024-06-04T20:15:02ZAlternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cellsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c7f4abf8-2f57-4c09-9ff6-037b4bf28911EnglishJisc Publications RouterNature Research2024Carrelha, JMazzi, SWinroth, AHagemann-Jensen, MZiegenhain, CHögstrand, KSeki, MBrennan, MSLehander, MWu, BMeng, YMarkljung, ENorfo, RIshida, HBelander Strålin, KGrasso, FSimoglou Karali, CAliouat, AHillen, AChari, ESiletti, KThongjuea, SMead, AJLinnarsson, SNerlov, CJacobsen, SEWRare multipotent stem cells replenish millions of blood cells per second through a time-consuming process, passing through multiple stages of increasingly lineage-restricted progenitors. Although insults to the blood-forming system highlight the need for more rapid blood replenishment from stem cells, established models of hematopoiesis implicate only one mandatory differentiation pathway for each blood cell lineage. Here, we establish a nonhierarchical relationship between distinct stem cells that replenish all blood cell lineages and stem cells that replenish almost exclusively platelets, a lineage essential for hemostasis and with important roles in both the innate and adaptive immune systems. These distinct stem cells use cellularly, molecularly and functionally separate pathways for the replenishment of molecularly distinct megakaryocyte-restricted progenitors: a slower steady-state multipotent pathway and a fast-track emergency-activated platelet-restricted pathway. These findings provide a framework for enhancing platelet replenishment in settings in which slow recovery of platelets remains a major clinical challenge. |
| spellingShingle | Carrelha, J Mazzi, S Winroth, A Hagemann-Jensen, M Ziegenhain, C Högstrand, K Seki, M Brennan, MS Lehander, M Wu, B Meng, Y Markljung, E Norfo, R Ishida, H Belander Strålin, K Grasso, F Simoglou Karali, C Aliouat, A Hillen, A Chari, E Siletti, K Thongjuea, S Mead, AJ Linnarsson, S Nerlov, C Jacobsen, SEW Alternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cells |
| title | Alternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cells |
| title_full | Alternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cells |
| title_fullStr | Alternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cells |
| title_full_unstemmed | Alternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cells |
| title_short | Alternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cells |
| title_sort | alternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cells |
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