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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat
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Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat

机译：鉴定存在于骨骼肌和白色脂肪中的诱导型褐色脂肪细胞祖细胞

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摘要

Brown fat is specialized for energy expenditure and has therefore been proposed to function as a defense against obesity. Despite recent advances in delineating the transcriptional regulation of brown adipocyte differentiation, cellular lineage specification and developmental cues specifying brown-fat cell fate remain poorly understood. In this study, we identify and isolate a subpopulation of adipogenic progenitors (Sca-1~+/CD45~-/Mac1~-; referred to as Sca-1~+ progenitor cells, ScaPCs) residing in murine brown fat, white fat, and skeletal muscle. ScaPCs derived from different tissues possess unique molecular expression signatures and adipogenic capacities. Importantly, although the ScaPCs from interscapular brown adipose tissue (BAT) are constitutively committed brown-fat progenitors, Sca-1~+ cells from skeletal muscle and subcutaneous white fat are highly inducible to differentiate into brown-like adipocytes upon stimulation with bone morphogenetic protein 7 (BMP7). Consistent with these findings, human preadipocytes isolated from subcutaneous white fat also exhibit the greatest inducible capacity to become brown adipocytes compared with cells isolated from mesenteric or omental white fat. When muscle-resident ScaPCs are re-engrafted into skeletal muscle of syngeneic mice, BMP7-treated ScaPCs efficiently develop into adipose tissue with brown fat-specific characteristics. Importantly, ScaPCs from obesity-resistant mice exhibit markedly higher thermogenic capacity compared with cells isolated from obesity-prone mice. These data establish the molecular characteristics of tissue-resident adipose progenitors and demonstrate a dynamic interplay between these progenitors and inductive signals that act in concert to specify brown adipocyte development.
机译：棕色脂肪专门用于能量消耗，因此已被提议作为抵抗肥胖的防御物。尽管最近在描述棕色脂肪细胞分化的转录调控方面取得了进展，但是对细胞谱系的规范和发育线索表明了棕色脂肪细胞的命运仍然知之甚少。在这项研究中，我们鉴定并分离出了鼠脂肪，白脂肪，脂肪族祖细胞（Sca-1〜+ / CD45〜-/ Mac1〜-，称为Sca-1〜+祖细胞，ScaPCs）的亚群。和骨骼肌。来自不同组织的ScaPC具有独特的分子表达特征和成脂能力。重要的是，尽管肩s间棕色脂肪组织（BAT）的ScaPCs是组成型定型的棕色脂肪祖细胞，但是在骨骼形态发生蛋白刺激下，骨骼肌和皮下白色脂肪的Sca-1〜+细胞可高度诱导分化为棕色样脂肪细胞7（BMP7）。与这些发现一致的是，与从肠系膜或网膜白色脂肪分离的细胞相比，从皮下白色脂肪分离的人前脂肪细胞也表现出最大的诱导能力，成为棕色脂肪细胞。当驻留于肌肉的ScaPCs重新移植到同系小鼠的骨骼肌中时，经BMP7处理的ScaPCs有效地发育为具有棕色脂肪特异性特征的脂肪组织。重要的是，与肥胖易感小鼠相比，来自肥胖抗性小鼠的ScaPC具有显着更高的产热能力。这些数据建立了组织驻留脂肪祖细胞的分子特征，并证明了这些祖细胞与诱导信号协同作用以指定棕色脂肪细胞发育的动态相互作用。

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    Tim J. Schulz; Tian Lian Huang; Thien T. Tran; Hongbin Zhang; Kristy L. Townsend; Jennifer L Shadrach; Massimiliano Cerletti; Lindsay E. McDougall; Nino Giorgadze; Tamara Tchkonia; Denis Schrier; Dean Falb; James L Kirkland; Amy J. Wagers; Yu-Hua Tseng;

  • 作者单位

    The Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215,Harvard Stem Cell Institute, Boston, MA 02215;

    The Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215;

    The Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215;

    The Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215;

    The Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215;

    The Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215,Harvard Stem Cell Institute, Boston, MA 02215,Department of Stem Cell and Regenerative Biology, Harvard University, MA 02138,The Howard Hughes Medical Institute and Cambridge, MA 02138;

    The Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215,Harvard Stem Cell Institute, Boston, MA 02215,Department of Stem Cell and Regenerative Biology, Harvard University, MA 02138;

    The Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215;

    The Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905;

    The Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905;

    Stryker Biotech, Hopkinton, MA 01748;

    Stryker Biotech, Hopkinton, MA 01748;

    The Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905;

    The Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215,Harvard Stem Cell Institute, Boston, MA 02215,Department of Stem Cell and Regenerative Biology, Harvard University, MA 02138,The Howard Hughes Medical Institute and Cambridge, MA 02138;

    The Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215,Harvard Stem Cell Institute, Boston, MA 02215;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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