박준영 (University of California, Los Angeles)

한빛사논문

조회551

University of California, Los Angeles

CV File 101 kb

Cell, Nov 28 2023, S0092-8674(23)01228-X | https://doi.org/10.1016/j.cell.2023.11.011 Atlas of fetal metabolism during mid-to-late gestation and diabetic pregnancy

Cesar A. Perez-Ramirez,^1,4,8 Haruko Nakano,^2,8 Richard C. Law,³ Nedas Matulionis,¹ Jennifer Thompson,²Andrew Pfeiffer,¹ Junyoung O. Park,^3,5,6,9 Atsushi Nakano,^2,4,6,7,9,* and Heather R. Christofk^{1,4,5,6,9,10,*}

¹Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA
²Department of Molecular, Cell, and Developmental Biology, UCLA, Los Angeles, CA 90095, USA
³Department of Chemical and Biomolecular Engineering, UCLA, Los Angeles, CA 90095, USA
⁴Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA
⁵Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA
⁶Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA
⁷Department of Cell Physiology, The Jikei University School of Medicine, Tokyo, Japan
⁸These authors contributed equally
⁹Senior author
¹⁰Lead contact

^*Corresponding authors: correspondence to Atsushi Nakano or Heather R. Christofk

Abstract

Mounting evidence suggests metabolism instructs stem cell fate decisions. However, how fetal metabolism changes during development and how altered maternal metabolism shapes fetal metabolism remain unexplored. We present a descriptive atlas of in vivo fetal murine metabolism during mid-to-late gestation in normal and diabetic pregnancy. Using ¹³C-glucose and liquid chromatography-mass spectrometry (LC-MS), we profiled the metabolism of fetal brains, hearts, livers, and placentas harvested from pregnant dams between embryonic days (E)10.5 and 18.5. Our analysis revealed metabolic features specific to a hyperglycemic environment and signatures that may denote developmental transitions during euglycemic development. We observed sorbitol accumulation in fetal tissues and altered neurotransmitter levels in fetal brains isolated from hyperglycemic dams. Tracing ¹³C-glucose revealed disparate fetal nutrient sourcing depending on maternal glycemic states. Regardless of glycemic state, histidine-derived metabolites accumulated in late-stage fetal tissues. Our rich dataset presents a comprehensive overview of in vivo fetal tissue metabolism and alterations due to maternal hyperglycemia.

논문정보

형식Research article
게재일2023년 11월 (BRIC 등록일 2023-12-11)
연구진국외 연구진
분야 생명과학 > 생화학

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