Dermatopontin in Bone Marrow Extracellular Matrix Regulates Adherence but Is Dispensable for Murine Hematopoietic Cell Maintenance

Ashley C. Kramer; Amanda L. Blake; Mandy E. Taisto; Michael J. Lehrke; Beau R Webber; Troy C Lund

doi:10.1016/j.stemcr.2017.07.021

Dermatopontin in Bone Marrow Extracellular Matrix Regulates Adherence but Is Dispensable for Murine Hematopoietic Cell Maintenance

Ashley C. Kramer, Amanda L. Blake, Mandy E. Taisto, Michael J. Lehrke, Beau R Webber, Troy C Lund

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

7 Scopus citations

Abstract

The hematopoietic marrow microenvironment is composed of multiple cell types embedded in an extracellular matrix (ECM). We have explored marrow ECM using mass spectrometry and found dermatopontin (DPT), a small non-collagenous ECM protein, to be present. We found that DPT cooperates with other ECM proteins to promote hematopoietic cell adherence in vitro on plastic as well as OP9 stromal cells. We generated constitutional DPT^−/− mice that were viable and had no peripheral lympho-hematopoietic abnormalities. The composition of the marrow of wild-type and DPT^−/− mice was equivalent in terms of cellularity, CFU-C, LSK (Lineage⁻, SCA-1⁺, KIT⁺), and LSK-SLAM (LSK, CD48⁻, CD150⁺) frequencies. These data suggest that DPT fosters adherence but is not required for steady-state hematopoiesis in vivo. There are likely overlapping cellular adhesion mechanisms that can compensate to maintain the hematopoietic niche in the absence of DPT.

Original language	English (US)
Pages (from-to)	770-778
Number of pages	9
Journal	Stem Cell Reports
Volume	9
Issue number	3
DOIs	https://doi.org/10.1016/j.stemcr.2017.07.021
State	Published - Sep 12 2017

Bibliographical note

Funding Information:
We gratefully acknowledge the Mouse Genetics Core Facility at the University of Minnesota Cancer Center. T.C.L. had grant support from the National Heart, Lung, and Blood Institute ( K08HL108998 , R03HL133318 ), the American Association of Blood Banks/National Blood Foundation , Regenerative Medicine Minnesota , and an American Society of Hematology Scholar Award. B.R.W. had support from the National Heart, Lung, and Blood Institute ( T32-HL007062 ).

Publisher Copyright:
© 2017 The Author(s)

Keywords

decellularization
dermatopontin
extracellular matrix
hematopoiesis
hematopoietic niche

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10.1016/j.stemcr.2017.07.021

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599243

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title = "Dermatopontin in Bone Marrow Extracellular Matrix Regulates Adherence but Is Dispensable for Murine Hematopoietic Cell Maintenance",

abstract = "The hematopoietic marrow microenvironment is composed of multiple cell types embedded in an extracellular matrix (ECM). We have explored marrow ECM using mass spectrometry and found dermatopontin (DPT), a small non-collagenous ECM protein, to be present. We found that DPT cooperates with other ECM proteins to promote hematopoietic cell adherence in vitro on plastic as well as OP9 stromal cells. We generated constitutional DPT−/− mice that were viable and had no peripheral lympho-hematopoietic abnormalities. The composition of the marrow of wild-type and DPT−/− mice was equivalent in terms of cellularity, CFU-C, LSK (Lineage−, SCA-1+, KIT+), and LSK-SLAM (LSK, CD48−, CD150+) frequencies. These data suggest that DPT fosters adherence but is not required for steady-state hematopoiesis in vivo. There are likely overlapping cellular adhesion mechanisms that can compensate to maintain the hematopoietic niche in the absence of DPT.",

keywords = "decellularization, dermatopontin, extracellular matrix, hematopoiesis, hematopoietic niche",

author = "Kramer, {Ashley C.} and Blake, {Amanda L.} and Taisto, {Mandy E.} and Lehrke, {Michael J.} and Webber, {Beau R} and Lund, {Troy C}",

note = "Funding Information: We gratefully acknowledge the Mouse Genetics Core Facility at the University of Minnesota Cancer Center. T.C.L. had grant support from the National Heart, Lung, and Blood Institute ( K08HL108998 , R03HL133318 ), the American Association of Blood Banks/National Blood Foundation , Regenerative Medicine Minnesota , and an American Society of Hematology Scholar Award. B.R.W. had support from the National Heart, Lung, and Blood Institute ( T32-HL007062 ). Publisher Copyright: {\textcopyright} 2017 The Author(s)",

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AU - Webber, Beau R

AU - Lund, Troy C

N1 - Funding Information: We gratefully acknowledge the Mouse Genetics Core Facility at the University of Minnesota Cancer Center. T.C.L. had grant support from the National Heart, Lung, and Blood Institute ( K08HL108998 , R03HL133318 ), the American Association of Blood Banks/National Blood Foundation , Regenerative Medicine Minnesota , and an American Society of Hematology Scholar Award. B.R.W. had support from the National Heart, Lung, and Blood Institute ( T32-HL007062 ). Publisher Copyright: © 2017 The Author(s)

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N2 - The hematopoietic marrow microenvironment is composed of multiple cell types embedded in an extracellular matrix (ECM). We have explored marrow ECM using mass spectrometry and found dermatopontin (DPT), a small non-collagenous ECM protein, to be present. We found that DPT cooperates with other ECM proteins to promote hematopoietic cell adherence in vitro on plastic as well as OP9 stromal cells. We generated constitutional DPT−/− mice that were viable and had no peripheral lympho-hematopoietic abnormalities. The composition of the marrow of wild-type and DPT−/− mice was equivalent in terms of cellularity, CFU-C, LSK (Lineage−, SCA-1+, KIT+), and LSK-SLAM (LSK, CD48−, CD150+) frequencies. These data suggest that DPT fosters adherence but is not required for steady-state hematopoiesis in vivo. There are likely overlapping cellular adhesion mechanisms that can compensate to maintain the hematopoietic niche in the absence of DPT.

AB - The hematopoietic marrow microenvironment is composed of multiple cell types embedded in an extracellular matrix (ECM). We have explored marrow ECM using mass spectrometry and found dermatopontin (DPT), a small non-collagenous ECM protein, to be present. We found that DPT cooperates with other ECM proteins to promote hematopoietic cell adherence in vitro on plastic as well as OP9 stromal cells. We generated constitutional DPT−/− mice that were viable and had no peripheral lympho-hematopoietic abnormalities. The composition of the marrow of wild-type and DPT−/− mice was equivalent in terms of cellularity, CFU-C, LSK (Lineage−, SCA-1+, KIT+), and LSK-SLAM (LSK, CD48−, CD150+) frequencies. These data suggest that DPT fosters adherence but is not required for steady-state hematopoiesis in vivo. There are likely overlapping cellular adhesion mechanisms that can compensate to maintain the hematopoietic niche in the absence of DPT.

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Dermatopontin in Bone Marrow Extracellular Matrix Regulates Adherence but Is Dispensable for Murine Hematopoietic Cell Maintenance

Abstract

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