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

4 Scopus citations

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 (US)
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

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

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10.1016/j.stemcr.2022.10.003

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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

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

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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",

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year = "2022",

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

language = "English (US)",

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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.

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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

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ER -

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

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Keywords

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