Evidence map›Paper›PMID 25904599›Full record

ArticleCirculation research2015

Functional analysis and transcriptomic profiling of iPSC-derived macrophages and their application in modeling Mendelian disease.

Hanrui Zhang, Chenyi Xue, Rhia Shah, Kate Bermingham, Christine C Hinkle, Wenjun Li, Amrith Rodrigues, Jennifer Tabita-Martinez, John S Millar, Marina Cuchel and 12 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 1 pooled it
5.1field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

88 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.

  1. Meta-Analysis ofFrontiers in immunology · 2019
    Pooled it
  2. Trial
  3. Review
  4. Review
  5. Article
  6. Article
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  8. High-throughput screening of small molecules targetingAntimicrobial agents and chemotherapy · 2025
    Article
  9. Article
  10. Review
  11. Review
  12. Article
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  15. Macrophage WDFY3, a protector against autoimmunity.bioRxiv : the preprint server for biology · 2024
    Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

28 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 2 institutions in 1 country.

Hanrui ZhangFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
Chenyi XueFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
Rhia ShahFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
Kate BerminghamFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
Christine C HinkleFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
Wenjun LiFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
Amrith RodriguesFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
Jennifer Tabita-MartinezFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
John S MillarFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
Marina CuchelFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
Evanthia E PashosFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
Ying LiuFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
Ruilan YanFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
Wenli YangFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
Sager J GosaiFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
Daniel VanDornFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
Stella T ChouFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
Brian D GregoryFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
Edward E MorriseyFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
Mingyao LiFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
Daniel J RaderFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.).
Muredach P ReillyFrom the Cardiovascular Institute (H.Z., C.X., R.S., K.B., C.C.H., W.L., A.R., J.T.-M., E.E.P., E.E.M., D.J.R., M.P.R.), and Department of Biostatistics and Epidemiology (M.L.), Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Institute for Diabetes, Obesity, and Metabolism (A.R., M.C., E.E.P., D.J.R.), Department of Medicine, Metabolic Tracer Resource, Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Institute for Regenerative Medicine (Y.L., R.Y., W.Y., E.E.M.), Department of Biology, Perelman School of Medicine and School of Arts and Science (S.J.G., B.D.G.), PENN Genome Frontiers Institute (S.J.G., B.D.G.), Department of Pediatrics, Perelman School of Medicine (S.T.C.), Department of Cell and Developmental Biology, Perelman School of Medicine (E.E.M.), and Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; and Division of Hematology, The Children's Hospital of Philadelphia, PA (D.V., S.T.C.). muredach@mail.med.upenn.edu.
University of Pennsylvania · USCardiovascular Institute of the South · US

Funding

iPS-derived hepatocytes for interrogation of lipid phenotypesU01HG006398 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI RADER, DANIEL JAMES · 2011 to 2015
$8.6M
Elucidation of Tissue-Specific Transcriptomic Profiles in Cardiometabolic DiseaseR01HL113147 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI LI, MINGYAO, REILLY, MUREDACH P · 2012 to 2022
$6.8M
Fractalkine in Adipose Inflammation and Insulin ResistanceR01DK090505 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI REILLY, MUREDACH P · 2011 to 2015
$2.8M
Translational Studies of ADAMTS7 a Novel GWAS Locus for Coronary AtherosclerosisR01HL111694 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI REILLY, MUREDACH P · 2012 to 2015
$2.4M
Glycomics of Heart and Lung Disease in the Genomic EraU01HL108636 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI REILLY, MUREDACH P · 2011 to 2014
$2.4M
Mentored Patient Oriented Research in Cardiometabolic DiseaseK24HL107643 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI REILLY, MUREDACH P · 2011 to 2020
$1.4M
NHGRI NIH HHS U01 HG006398NHGRI NIH HHS U01-HG006398NHLBI NIH HHS K24 HL107643NHLBI NIH HHS K24-HL-107643NHLBI NIH HHS R01 HL111694NHLBI NIH HHS R01-HL-111694NHLBI NIH HHS R01 HL113147NHLBI NIH HHS R01-HL-113147NHLBI NIH HHS U01 HL108636NHLBI NIH HHS U01-HL-108636NIDDK NIH HHS R01 DK090505NIDDK NIH HHS R01-DK-090505
6 · The paper itself

Abstract

rationaleAn efficient and reproducible source of genotype-specific human macrophages is essential for study of human macrophage biology and related diseases.

objectiveTo perform integrated functional and transcriptome analyses of human induced pluripotent stem cell-derived macrophages (IPSDMs) and their isogenic human peripheral blood mononuclear cell-derived macrophage (HMDM) counterparts and assess the application of IPSDM in modeling macrophage polarization and Mendelian disease. METHODS AND

resultsWe developed an efficient protocol for differentiation of IPSDM, which expressed macrophage-specific markers and took up modified lipoproteins in a similar manner to HMDM. Like HMDM, IPSDM revealed reduction in phagocytosis, increase in cholesterol efflux capacity and characteristic secretion of inflammatory cytokines in response to M1 (lipopolysaccharide+interferon-γ) activation. RNA-Seq revealed that nonpolarized (M0) as well as M1 or M2 (interleukin-4) polarized IPSDM shared transcriptomic profiles with their isogenic HMDM counterparts while also revealing novel markers of macrophage polarization. Relative to IPSDM and HMDM of control individuals, patterns of defective cholesterol efflux to apolipoprotein A-I and high-density lipoprotein-3 were qualitatively and quantitatively similar in IPSDM and HMDM of patients with Tangier disease, an autosomal recessive disorder because of mutations in ATP-binding cassette transporter AI. Tangier disease-IPSDM also revealed novel defects of enhanced proinflammatory response to lipopolysaccharide stimulus.

conclusionsOur protocol-derived IPSDM are comparable with HMDM at phenotypic, functional, and transcriptomic levels. Tangier disease-IPSDM recapitulated hallmark features observed in HMDM and revealed novel inflammatory phenotypes. IPSDMs provide a powerful tool for study of macrophage-specific function in human genetic disorders as well as molecular studies of human macrophage activation and polarization.

Indexed as

Cell Culture TechniquesTranscriptomeAdultAgedAnimalsAntigens, DifferentiationATP Binding Cassette Transporter 1Base SequenceCell DifferentiationCells, CulturedCholesterolEmbryoid BodiesFemaleGenotypeHumansInduced Pluripotent Stem CellsABCA1 protein, humanAbca1 protein, mouseAntigens, DifferentiationATP Binding Cassette Transporter 1CholesterolInterferon-gammaLipopolysaccharidesRNA, Messengercholesterolgenomicsinduced pluripotent stem cellsinflammationmacrophages

Identifiers

PMID25904599
PMCPMC4565503
OpenAlexW2065561900

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