Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan

Zhi-Jian Liu, Karin M. Hoffmeister, Zhongbo Hu, Donald E. Mager, Sihem Ait-Oudhia, Marlyse A. Debrincat, Irina Pleines, Emma C. Josefsson, Benjamin T. Kile, Joseph Italiano Jr, Haley Ramsey, Renata Grozovsky, Peter Veng-Pedersen, Chaitanya Chavda, Martha Sola-Visner

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The fetal/neonatal hematopoietic system must generate enough blood cells to meet the demands of rapid growth. This unique challenge might underlie the high incidence of thrombocytopenia among preterm neonates. In this study, neonatal platelet production and turnover were investigated in newborn mice. Based on a combination of blood volume expansion and increasing platelet counts, the platelet mass increased sevenfold during the first 2 weeks of murine life, a time during which thrombopoiesis shifted from liver to bone marrow. Studies applying in vivo biotinylation and mathematical modeling showed that newborn and adult mice had similar platelet production rates, but neonatal platelets survived 1 day longer in circulation. This prolonged lifespan fully accounted for the rise in platelet counts observed during the second week of murine postnatal life. A study of pro-apoptotic and anti-apoptotic Bcl-2 family proteins showed that neonatal platelets had higher levels of the anti-apoptotic protein Bcl-2 and were more resistant to apoptosis induced by the Bcl-2/Bcl-xL inhibitor ABT-737 than adult platelets. However, genetic ablation or pharmacologic inhibition of Bcl-2 alone did not shorten neonatal platelet survival or reduce platelet counts in newborn mice, indicating the existence of redundant or alternative mechanisms mediating the prolonged lifespan of neonatal platelets.

Original languageEnglish
Pages (from-to)3381-3389
Number of pages9
JournalBlood
Volume123
Issue number22
DOIs
Publication statusPublished - 29 May 2014
Externally publishedYes

Cite this

Liu, Z-J., Hoffmeister, K. M., Hu, Z., Mager, D. E., Ait-Oudhia, S., Debrincat, M. A., ... Sola-Visner, M. (2014). Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan. Blood, 123(22), 3381-3389. https://doi.org/10.1182/blood-2013-06-508200
Liu, Zhi-Jian ; Hoffmeister, Karin M. ; Hu, Zhongbo ; Mager, Donald E. ; Ait-Oudhia, Sihem ; Debrincat, Marlyse A. ; Pleines, Irina ; Josefsson, Emma C. ; Kile, Benjamin T. ; Italiano Jr, Joseph ; Ramsey, Haley ; Grozovsky, Renata ; Veng-Pedersen, Peter ; Chavda, Chaitanya ; Sola-Visner, Martha . / Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan. In: Blood. 2014 ; Vol. 123, No. 22. pp. 3381-3389.
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title = "Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan",
abstract = "The fetal/neonatal hematopoietic system must generate enough blood cells to meet the demands of rapid growth. This unique challenge might underlie the high incidence of thrombocytopenia among preterm neonates. In this study, neonatal platelet production and turnover were investigated in newborn mice. Based on a combination of blood volume expansion and increasing platelet counts, the platelet mass increased sevenfold during the first 2 weeks of murine life, a time during which thrombopoiesis shifted from liver to bone marrow. Studies applying in vivo biotinylation and mathematical modeling showed that newborn and adult mice had similar platelet production rates, but neonatal platelets survived 1 day longer in circulation. This prolonged lifespan fully accounted for the rise in platelet counts observed during the second week of murine postnatal life. A study of pro-apoptotic and anti-apoptotic Bcl-2 family proteins showed that neonatal platelets had higher levels of the anti-apoptotic protein Bcl-2 and were more resistant to apoptosis induced by the Bcl-2/Bcl-xL inhibitor ABT-737 than adult platelets. However, genetic ablation or pharmacologic inhibition of Bcl-2 alone did not shorten neonatal platelet survival or reduce platelet counts in newborn mice, indicating the existence of redundant or alternative mechanisms mediating the prolonged lifespan of neonatal platelets.",
author = "Zhi-Jian Liu and Hoffmeister, {Karin M.} and Zhongbo Hu and Mager, {Donald E.} and Sihem Ait-Oudhia and Debrincat, {Marlyse A.} and Irina Pleines and Josefsson, {Emma C.} and Kile, {Benjamin T.} and {Italiano Jr}, Joseph and Haley Ramsey and Renata Grozovsky and Peter Veng-Pedersen and Chaitanya Chavda and Martha Sola-Visner",
year = "2014",
month = "5",
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doi = "10.1182/blood-2013-06-508200",
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journal = "Blood",
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Liu, Z-J, Hoffmeister, KM, Hu, Z, Mager, DE, Ait-Oudhia, S, Debrincat, MA, Pleines, I, Josefsson, EC, Kile, BT, Italiano Jr, J, Ramsey, H, Grozovsky, R, Veng-Pedersen, P, Chavda, C & Sola-Visner, M 2014, 'Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan' Blood, vol. 123, no. 22, pp. 3381-3389. https://doi.org/10.1182/blood-2013-06-508200

Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan. / Liu, Zhi-Jian; Hoffmeister, Karin M.; Hu, Zhongbo; Mager, Donald E.; Ait-Oudhia, Sihem; Debrincat, Marlyse A.; Pleines, Irina ; Josefsson, Emma C.; Kile, Benjamin T.; Italiano Jr, Joseph; Ramsey, Haley ; Grozovsky, Renata ; Veng-Pedersen, Peter; Chavda, Chaitanya; Sola-Visner, Martha .

In: Blood, Vol. 123, No. 22, 29.05.2014, p. 3381-3389.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan

AU - Liu, Zhi-Jian

AU - Hoffmeister, Karin M.

AU - Hu, Zhongbo

AU - Mager, Donald E.

AU - Ait-Oudhia, Sihem

AU - Debrincat, Marlyse A.

AU - Pleines, Irina

AU - Josefsson, Emma C.

AU - Kile, Benjamin T.

AU - Italiano Jr, Joseph

AU - Ramsey, Haley

AU - Grozovsky, Renata

AU - Veng-Pedersen, Peter

AU - Chavda, Chaitanya

AU - Sola-Visner, Martha

PY - 2014/5/29

Y1 - 2014/5/29

N2 - The fetal/neonatal hematopoietic system must generate enough blood cells to meet the demands of rapid growth. This unique challenge might underlie the high incidence of thrombocytopenia among preterm neonates. In this study, neonatal platelet production and turnover were investigated in newborn mice. Based on a combination of blood volume expansion and increasing platelet counts, the platelet mass increased sevenfold during the first 2 weeks of murine life, a time during which thrombopoiesis shifted from liver to bone marrow. Studies applying in vivo biotinylation and mathematical modeling showed that newborn and adult mice had similar platelet production rates, but neonatal platelets survived 1 day longer in circulation. This prolonged lifespan fully accounted for the rise in platelet counts observed during the second week of murine postnatal life. A study of pro-apoptotic and anti-apoptotic Bcl-2 family proteins showed that neonatal platelets had higher levels of the anti-apoptotic protein Bcl-2 and were more resistant to apoptosis induced by the Bcl-2/Bcl-xL inhibitor ABT-737 than adult platelets. However, genetic ablation or pharmacologic inhibition of Bcl-2 alone did not shorten neonatal platelet survival or reduce platelet counts in newborn mice, indicating the existence of redundant or alternative mechanisms mediating the prolonged lifespan of neonatal platelets.

AB - The fetal/neonatal hematopoietic system must generate enough blood cells to meet the demands of rapid growth. This unique challenge might underlie the high incidence of thrombocytopenia among preterm neonates. In this study, neonatal platelet production and turnover were investigated in newborn mice. Based on a combination of blood volume expansion and increasing platelet counts, the platelet mass increased sevenfold during the first 2 weeks of murine life, a time during which thrombopoiesis shifted from liver to bone marrow. Studies applying in vivo biotinylation and mathematical modeling showed that newborn and adult mice had similar platelet production rates, but neonatal platelets survived 1 day longer in circulation. This prolonged lifespan fully accounted for the rise in platelet counts observed during the second week of murine postnatal life. A study of pro-apoptotic and anti-apoptotic Bcl-2 family proteins showed that neonatal platelets had higher levels of the anti-apoptotic protein Bcl-2 and were more resistant to apoptosis induced by the Bcl-2/Bcl-xL inhibitor ABT-737 than adult platelets. However, genetic ablation or pharmacologic inhibition of Bcl-2 alone did not shorten neonatal platelet survival or reduce platelet counts in newborn mice, indicating the existence of redundant or alternative mechanisms mediating the prolonged lifespan of neonatal platelets.

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U2 - 10.1182/blood-2013-06-508200

DO - 10.1182/blood-2013-06-508200

M3 - Article

VL - 123

SP - 3381

EP - 3389

JO - Blood

JF - Blood

SN - 0006-4971

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Liu Z-J, Hoffmeister KM, Hu Z, Mager DE, Ait-Oudhia S, Debrincat MA et al. Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan. Blood. 2014 May 29;123(22):3381-3389. https://doi.org/10.1182/blood-2013-06-508200