Maternal Western-style diet remodels the transcriptional landscape of fetal hematopoietic stem and progenitor cells in rhesus macaques

Suhas Sureshchandra; Chi N. Chan; Jacob J. Robino; Lindsay K. Parmelee; Michael J. Nash; Stephanie R. Wesolowski; Eric M. Pietras; Jacob E. Friedman; Diana Takahashi; Weining Shen; Xiwen Jiang; Jon D. Hennebold; Devorah Goldman; William Packwood; Jonathan R. Lindner; Charles T. Roberts; Benjamin J. Burwitz; Ilhem Messaoudi; Oleg Varlamov

doi:10.1016/j.stemcr.2022.10.003

Maternal Western-style diet remodels the transcriptional landscape of fetal hematopoietic stem and progenitor cells in rhesus macaques

Suhas Sureshchandra
, Chi N. Chan
, Jacob J. Robino
, Lindsay K. Parmelee
, Michael J. Nash
, Stephanie R. Wesolowski
, Eric M. Pietras
, Jacob E. Friedman
, Diana Takahashi
, Weining Shen
, Xiwen Jiang
, Jon D. Hennebold
, Devorah Goldman
, William Packwood
, Jonathan R. Lindner
, Charles T. Roberts
, Benjamin J. Burwitz
, Ilhem Messaoudi
, Oleg Varlamov

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

17 Citations (SciVal)

Abstract

Maternal obesity adversely impacts the in utero metabolic environment, but its effect on fetal hematopoiesis remains incompletely understood. During late development, the fetal bone marrow (FBM) becomes the major site where macrophages and B lymphocytes are produced via differentiation of hematopoietic stem and progenitor cells (HSPCs). Here, we analyzed the transcriptional landscape of FBM HSPCs at single-cell resolution in fetal macaques exposed to a maternal high-fat Western-style diet (WSD) or a low-fat control diet. We demonstrate that maternal WSD induces a proinflammatory response in FBM HSPCs and fetal macrophages. In addition, maternal WSD consumption suppresses the expression of B cell development genes and decreases the frequency of FBM B cells. Finally, maternal WSD leads to poor engraftment of fetal HSPCs in nonlethally irradiated immunodeficient NOD/SCID/IL2rγ^−/− mice. Collectively, these data demonstrate for the first time that maternal WSD impairs fetal HSPC differentiation and function in a translationally relevant nonhuman primate model.

Original language	English
Pages (from-to)	2595-2609
Number of pages	15
Journal	Stem Cell Reports
Volume	17
Issue number	12
DOIs	https://doi.org/10.1016/j.stemcr.2022.10.003
State	Published - Dec 13 2022

Bibliographical note

Publisher Copyright:
© 2022 The Author(s)

Funding

We thank Dr. Lauren Drew Martin for help with blood collections, Kati Marshall for help in animal handling and transplantation, Dr. Jennifer Atwood for assistance with cell sorting, and Dr. Melanie Oakes for assistance with library preparation and sequencing of 10x samples. This study was supported by NIH grants P50 HD071836 to C.T.R. and J.D.H., P51 OD01192 for operation of the ONPRC , 1R01AI142841 and 1R01AI145910 to I.M., R24-DK090964 to J.E.F., F30-DK122672 to M.J.N., R01-DK108910 to S.R.W., R01-DK119394 to E.M.P., and the shared instrumentation grant 1S10OD025002-01.

Funders	Funder number
National Institutes of Health (NIH)	P50 HD071836, P51 OD01192
National Institute of Allergy and Infectious F32-AI286447 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI168214 Jason W. Rosch Diseases National Institute of Allergy and Infectious P30 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R00-AI166116 Christopher D. Radka Diseases National Institute of Allergy and Infectious T32-AI106700 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI192221 Jason W. Rosch Diseases National Inst...	R01AI142841
Oregon National Primate Research Center	1R01AI142841, 1R01AI145910, 1S10OD025002-01, F30-DK122672, R01-DK119394, R24-DK090964, R01-DK108910

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

B lymphocytes
bone marrow
fetal development
hematopoietic stem and progenitor cells
high-fat diet
macrophages
maternal programming
monocytes
nonhuman primates
obesity

ASJC Scopus subject areas

Biochemistry
Genetics
Developmental Biology
Cell Biology

Access to Document

10.1016/j.stemcr.2022.10.003

Cite this

Sureshchandra, S., Chan, C. N., Robino, J. J., Parmelee, L. K., Nash, M. J., Wesolowski, S. R., Pietras, E. M., Friedman, J. E., Takahashi, D., Shen, W., Jiang, X., Hennebold, J. D., Goldman, D., Packwood, W., Lindner, J. R., Roberts, C. T., Burwitz, B. J., Messaoudi, I., & Varlamov, O. (2022). Maternal Western-style diet remodels the transcriptional landscape of fetal hematopoietic stem and progenitor cells in rhesus macaques. Stem Cell Reports, 17(12), 2595-2609. https://doi.org/10.1016/j.stemcr.2022.10.003

@article{34eea1815c4d4c25a9b5d81c1a2e02a8,

title = "Maternal Western-style diet remodels the transcriptional landscape of fetal hematopoietic stem and progenitor cells in rhesus macaques",

abstract = "Maternal obesity adversely impacts the in utero metabolic environment, but its effect on fetal hematopoiesis remains incompletely understood. During late development, the fetal bone marrow (FBM) becomes the major site where macrophages and B lymphocytes are produced via differentiation of hematopoietic stem and progenitor cells (HSPCs). Here, we analyzed the transcriptional landscape of FBM HSPCs at single-cell resolution in fetal macaques exposed to a maternal high-fat Western-style diet (WSD) or a low-fat control diet. We demonstrate that maternal WSD induces a proinflammatory response in FBM HSPCs and fetal macrophages. In addition, maternal WSD consumption suppresses the expression of B cell development genes and decreases the frequency of FBM B cells. Finally, maternal WSD leads to poor engraftment of fetal HSPCs in nonlethally irradiated immunodeficient NOD/SCID/IL2rγ−/− mice. Collectively, these data demonstrate for the first time that maternal WSD impairs fetal HSPC differentiation and function in a translationally relevant nonhuman primate model.",

keywords = "B lymphocytes, bone marrow, fetal development, hematopoietic stem and progenitor cells, high-fat diet, macrophages, maternal programming, monocytes, nonhuman primates, obesity",

author = "Suhas Sureshchandra and Chan, \{Chi N.\} and Robino, \{Jacob J.\} and Parmelee, \{Lindsay K.\} and Nash, \{Michael J.\} and Wesolowski, \{Stephanie R.\} and Pietras, \{Eric M.\} and Friedman, \{Jacob E.\} and Diana Takahashi and Weining Shen and Xiwen Jiang and Hennebold, \{Jon D.\} and Devorah Goldman and William Packwood and Lindner, \{Jonathan R.\} and Roberts, \{Charles T.\} and Burwitz, \{Benjamin J.\} and Ilhem Messaoudi and Oleg Varlamov",

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = dec,

day = "13",

doi = "10.1016/j.stemcr.2022.10.003",

language = "English",

volume = "17",

pages = "2595--2609",

number = "12",

}

Sureshchandra, S, Chan, CN, Robino, JJ, Parmelee, LK, Nash, MJ, Wesolowski, SR, Pietras, EM, Friedman, JE, Takahashi, D, Shen, W, Jiang, X, Hennebold, JD, Goldman, D, Packwood, W, Lindner, JR, Roberts, CT, Burwitz, BJ, Messaoudi, I & Varlamov, O 2022, 'Maternal Western-style diet remodels the transcriptional landscape of fetal hematopoietic stem and progenitor cells in rhesus macaques', Stem Cell Reports, vol. 17, no. 12, pp. 2595-2609. https://doi.org/10.1016/j.stemcr.2022.10.003

TY - JOUR

T1 - Maternal Western-style diet remodels the transcriptional landscape of fetal hematopoietic stem and progenitor cells in rhesus macaques

AU - Sureshchandra, Suhas

AU - Chan, Chi N.

AU - Robino, Jacob J.

AU - Parmelee, Lindsay K.

AU - Nash, Michael J.

AU - Wesolowski, Stephanie R.

AU - Pietras, Eric M.

AU - Friedman, Jacob E.

AU - Takahashi, Diana

AU - Shen, Weining

AU - Jiang, Xiwen

AU - Hennebold, Jon D.

AU - Goldman, Devorah

AU - Packwood, William

AU - Lindner, Jonathan R.

AU - Roberts, Charles T.

AU - Burwitz, Benjamin J.

AU - Messaoudi, Ilhem

AU - Varlamov, Oleg

PY - 2022/12/13

Y1 - 2022/12/13

N2 - Maternal obesity adversely impacts the in utero metabolic environment, but its effect on fetal hematopoiesis remains incompletely understood. During late development, the fetal bone marrow (FBM) becomes the major site where macrophages and B lymphocytes are produced via differentiation of hematopoietic stem and progenitor cells (HSPCs). Here, we analyzed the transcriptional landscape of FBM HSPCs at single-cell resolution in fetal macaques exposed to a maternal high-fat Western-style diet (WSD) or a low-fat control diet. We demonstrate that maternal WSD induces a proinflammatory response in FBM HSPCs and fetal macrophages. In addition, maternal WSD consumption suppresses the expression of B cell development genes and decreases the frequency of FBM B cells. Finally, maternal WSD leads to poor engraftment of fetal HSPCs in nonlethally irradiated immunodeficient NOD/SCID/IL2rγ−/− mice. Collectively, these data demonstrate for the first time that maternal WSD impairs fetal HSPC differentiation and function in a translationally relevant nonhuman primate model.

AB - Maternal obesity adversely impacts the in utero metabolic environment, but its effect on fetal hematopoiesis remains incompletely understood. During late development, the fetal bone marrow (FBM) becomes the major site where macrophages and B lymphocytes are produced via differentiation of hematopoietic stem and progenitor cells (HSPCs). Here, we analyzed the transcriptional landscape of FBM HSPCs at single-cell resolution in fetal macaques exposed to a maternal high-fat Western-style diet (WSD) or a low-fat control diet. We demonstrate that maternal WSD induces a proinflammatory response in FBM HSPCs and fetal macrophages. In addition, maternal WSD consumption suppresses the expression of B cell development genes and decreases the frequency of FBM B cells. Finally, maternal WSD leads to poor engraftment of fetal HSPCs in nonlethally irradiated immunodeficient NOD/SCID/IL2rγ−/− mice. Collectively, these data demonstrate for the first time that maternal WSD impairs fetal HSPC differentiation and function in a translationally relevant nonhuman primate model.

KW - B lymphocytes

KW - bone marrow

KW - fetal development

KW - hematopoietic stem and progenitor cells

KW - high-fat diet

KW - macrophages

KW - maternal programming

KW - monocytes

KW - nonhuman primates

KW - obesity

UR - https://www.scopus.com/pages/publications/85143883089

UR - https://www.scopus.com/pages/publications/85143883089#tab=citedBy

U2 - 10.1016/j.stemcr.2022.10.003

DO - 10.1016/j.stemcr.2022.10.003

M3 - Article

C2 - 36332628

AN - SCOPUS:85143883089

SN - 2213-6711

VL - 17

SP - 2595

EP - 2609

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 12

ER -

Maternal Western-style diet remodels the transcriptional landscape of fetal hematopoietic stem and progenitor cells in rhesus macaques

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this