Alternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cells

Joana Carrelha; Stefania Mazzi; Axel Winroth; Michael Hagemann-Jensen; Christoph Ziegenhain; Kari Högstrand; Masafumi Seki; Margs S. Brennan; Madeleine Lehander; Bishan Wu; Yiran Meng; Ellen Markljung; Ruggiero Norfo; Hisashi Ishida; Karin Belander Strålin; Francesca Grasso; Christina Simoglou Karali; Affaf Aliouat; Amy Hillen; Edwin Chari; Kimberly Siletti; Supat Thongjuea; Adam J. Mead; Sten Linnarsson; Claus Nerlov; Rickard Sandberg; Tetsuichi Yoshizato; Petter S. Woll; Sten Eirik W. Jacobsen

doi:10.1038/s41590-024-01845-6

Alternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cells

Joana Carrelha^*, Stefania Mazzi, Axel Winroth, Michael Hagemann-Jensen, Christoph Ziegenhain, Kari Högstrand, Masafumi Seki, Margs S. Brennan, Madeleine Lehander, Bishan Wu, Yiran Meng, Ellen Markljung, Ruggiero Norfo, Hisashi Ishida, Karin Belander Strålin, Francesca Grasso, Christina Simoglou Karali, Affaf Aliouat, Amy Hillen, Edwin ChariKimberly Siletti, Supat Thongjuea, Adam J. Mead, Sten Linnarsson, Claus Nerlov, Rickard Sandberg, Tetsuichi Yoshizato, Petter S. Woll, Sten Eirik W. Jacobsen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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.

Original language	English
Pages (from-to)	1007-1019
Number of pages	13
Journal	Nature immunology
Volume	25
Issue number	6
DOIs	https://doi.org/10.1038/s41590-024-01845-6
Publication status	Published - Jun 2024

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Carrelha, J., Mazzi, S., Winroth, A., Hagemann-Jensen, M., Ziegenhain, C., Högstrand, K., Seki, M., Brennan, M. S., Lehander, M., Wu, B., Meng, Y., Markljung, E., Norfo, R., Ishida, H., Belander Strålin, K., Grasso, F., Simoglou Karali, C., Aliouat, A., Hillen, A., ... Jacobsen, S. E. W. (2024). Alternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cells. Nature immunology, 25(6), 1007-1019. https://doi.org/10.1038/s41590-024-01845-6

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title = "Alternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cells",

abstract = "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.",

author = "Joana Carrelha and Stefania Mazzi and Axel Winroth and Michael Hagemann-Jensen and Christoph Ziegenhain and Kari H{\"o}gstrand and Masafumi Seki and Brennan, {Margs S.} and Madeleine Lehander and Bishan Wu and Yiran Meng and Ellen Markljung and Ruggiero Norfo and Hisashi Ishida and {Belander Str{\aa}lin}, Karin and Francesca Grasso and {Simoglou Karali}, Christina and Affaf Aliouat and Amy Hillen and Edwin Chari and Kimberly Siletti and Supat Thongjuea and Mead, {Adam J.} and Sten Linnarsson and Claus Nerlov and Rickard Sandberg and Tetsuichi Yoshizato and Woll, {Petter S.} and Jacobsen, {Sten Eirik W.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = jun,

doi = "10.1038/s41590-024-01845-6",

language = "English",

volume = "25",

pages = "1007--1019",

journal = "Nature immunology",

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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, Sandberg, R, Yoshizato, T, Woll, PS & Jacobsen, SEW 2024, 'Alternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cells', Nature immunology, vol. 25, no. 6, pp. 1007-1019. https://doi.org/10.1038/s41590-024-01845-6

TY - JOUR

T1 - Alternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cells

AU - Carrelha, Joana

AU - Mazzi, Stefania

AU - Winroth, Axel

AU - Hagemann-Jensen, Michael

AU - Ziegenhain, Christoph

AU - Högstrand, Kari

AU - Seki, Masafumi

AU - Brennan, Margs S.

AU - Lehander, Madeleine

AU - Wu, Bishan

AU - Meng, Yiran

AU - Markljung, Ellen

AU - Norfo, Ruggiero

AU - Ishida, Hisashi

AU - Belander Strålin, Karin

AU - Grasso, Francesca

AU - Simoglou Karali, Christina

AU - Aliouat, Affaf

AU - Hillen, Amy

AU - Chari, Edwin

AU - Siletti, Kimberly

AU - Thongjuea, Supat

AU - Mead, Adam J.

AU - Linnarsson, Sten

AU - Nerlov, Claus

AU - Sandberg, Rickard

AU - Yoshizato, Tetsuichi

AU - Woll, Petter S.

AU - Jacobsen, Sten Eirik W.

PY - 2024/6

Y1 - 2024/6

N2 - 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.

AB - 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.

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DO - 10.1038/s41590-024-01845-6

M3 - Article

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AN - SCOPUS:85194697875

SN - 1529-2908

VL - 25

SP - 1007

EP - 1019

JO - Nature immunology

JF - Nature immunology

IS - 6

ER -

Alternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cells

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