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Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

September 22, 2022

Article

Single-cell mapping of regenerative and fibrotic healing responses after musculoskeletal injury

  • Robert J. Tower,
  • Alec C. Bancroft,
  • Ashish R. Chowdary,
  • Spencer Barnes,
  • Nicole J. Edwards,
  • Chase A. Pagani,
  • Lindsay A. Dawson,
  • Benjamin Levi
First published:September 22, 2022
Tower et al. combine computational and histological approaches to explore the healing process after regenerative and fibrotic musculoskeletal injuries. This article points to transcriptional profiles correlating with healing outcome more than injury type or cell source and indicates unique inflammatory pathways activated in the fibroblast-like mesenchymal progenitor cells of each injury type. These multi-tissue analyses may help guide future therapeutic approaches to promote regenerative healing outcomes.
Article

PIM3-AMPK-HDAC4/5 axis restricts MuERVL-marked 2-cell-like state in embryonic stem cells

  • Xin Zhao,
  • Jian Shen,
  • Xuan Zhao,
  • Miao Zhang,
  • Xiao Feng,
  • Weiyu Zhang,
  • Xinyi Lu
First published:September 22, 2022
Zhao et al. discover the PIM3 signaling pathway as a key route to repress MuERVL and 2-cell-like totipotent state in ESCs. Pim3 loss allows phosphorylation of AMPK, which phosphorylates HDAC4/5 and promotes their transport out of the nucleus, thereby permitting acetylation of H3K9 and interfering with H3K9me1/2 deposition on MuERVL. Their findings provide a novel strategy to activate 2-cell-like totipotency.
Resource

Generation of a TPH2-EGFP reporter cell line for purification and monitoring of human serotonin neurons in vitro and in vivo

  • Ting Xu,
  • Jinjin Duan,
  • Yingqi Li,
  • Guanhao Wang,
  • Shuanqing Li,
  • You Li,
  • Wenting Lu,
  • Xinyi Yan,
  • Yixuan Ren,
  • Fei Guo,
  • Lining Cao,
  • Jianfeng Lu
First published:September 22, 2022
Dr. Lu and colleagues generate a TPH2-EGFP reporter system for human serotonin neurons (SNs). The reporter system enables scientists to detect electrophysiological features of SNs and to obtain purified SNs for transcriptional analysis and the study of pharmacological responses to antidepressants. This reporter system provides a versatile tool for the studies on human SNs-related development, drug screening, and cell replacement therapies.
Article

Age-related pathological impairments in directly reprogrammed dopaminergic neurons derived from patients with idiopathic Parkinson’s disease

  • Janelle Drouin-Ouellet,
  • Emilie M. Legault,
  • Fredrik Nilsson,
  • Karolina Pircs,
  • Julie Bouquety,
  • Florence Petit,
  • Shelby Shrigley,
  • Marcella Birtele,
  • Maria Pereira,
  • Petter Storm,
  • Yogita Sharma,
  • Andreas Bruzelius,
  • Romina Vuono,
  • Malin Kele,
  • Thomas B. Stoker,
  • Daniella Rylander Ottosson,
  • Anna Falk,
  • Johan Jakobsson,
  • Roger A. Barker,
  • Malin Parmar
First published:September 22, 2022
Drouin-Ouellet and colleagues have employed an efficient method to generate induced dopaminergic neurons derived from PD patients. These cells (unlike iPSC-derived dopaminergic neurons from these same patients) show age-related autophagy impairments that lead to an accumulation of phosphorylated alpha-synuclein. As such, this study presents a unique patient-specific model by which to study aged neuronal features relevant to idiopathic PD.
Article

Single-cell spatiotemporal analysis reveals cell fates and functions of transplanted mesenchymal stromal cells during bone repair

  • Chengyu Yang,
  • Zeshun Li,
  • Yang Liu,
  • Runpeng Hou,
  • Minmin Lin,
  • Linhao Fu,
  • Decheng Wu,
  • Quanying Liu,
  • Kai Li,
  • Chao Liu
First published:September 22, 2022
Mesenchymal stromal cell (MSC) transplantation could enhance bone repair, but their cell fate is poorly understood. In this article, Liu and colleagues utilize a single-cell 3D spatial correlation (sc3DSC) method to reveal that a large portion of transplanted MSCs maintain stemness, localize around blood vessels, increase blood vessel formation, and induce invasion of host progenitors into the bone defect.

September 8, 2022

Article

Space microgravity improves proliferation of human iPSC-derived cardiomyocytes

  • Antonio Rampoldi,
  • Parvin Forghani,
  • Dong Li,
  • Hyun Hwang,
  • Lawrence Christian Armand,
  • Jordan Fite,
  • Gene Boland,
  • Joshua Maxwell,
  • Kevin Maher,
  • Chunhui Xu
First published:September 08, 2022
In this article, Xu and colleagues show that cryopreserved 3D cardiac progenitors differentiated into highly enriched cardiomyocytes on the International Space Station (ISS). Compared with ISS 1G cells, ISS microgravity cells had increased proliferation and improved Ca2+ transients. Short-term microgravity also increased the expression of genes associated with proliferation and cardiac differentiation and contraction.
Article

In vitro modeling and rescue of ciliopathy associated with IQCB1/NPHP5 mutations using patient-derived cells

  • Kamil Kruczek,
  • Zepeng Qu,
  • Emily Welby,
  • Hiroko Shimada,
  • Suja Hiriyanna,
  • Milton A. English,
  • Wadih M. Zein,
  • Brian P. Brooks,
  • Anand Swaroop
First published:September 08, 2022
Swaroop and colleagues use in vitro disease modeling to characterize cilia abnormalities in human NPHP5-LCA patient-derived cells. Short photoreceptor outer segments with mislocalized opsin proteins and reduced CEP290 protein levels were observed in patient-derived retinal organoids. NPHP5-targeted gene therapy rescued the disease phenotypes in organoids, suggesting a key role of NPHP5 in stabilizing the CEP290-associated ciliary gate complex to ensure proper protein trafficking.
Article

Investigation of PTC124-mediated translational readthrough in a retinal organoid model of AIPL1-associated Leber congenital amaurosis

  • Amy Leung,
  • Almudena Sacristan-Reviriego,
  • Pedro R.L. Perdigão,
  • Hali Sai,
  • Michalis Georgiou,
  • Angelos Kalitzeos,
  • Amanda-Jayne F. Carr,
  • Peter J. Coffey,
  • Michel Michaelides,
  • James Bainbridge,
  • Michael E. Cheetham,
  • Jacqueline van der Spuy
First published:September 08, 2022
Leung et al. isolated renal epithelial cells from affected children to model severe AIPL1-associated retinal disease through iPSC retinal organogenesis. Although PTC124-mediated translational readthrough of a common AIPL1 nonsense mutation rescued low levels of full-length AIPL1 in retinal organoids from affected individuals compared with CRISPR-Cas9-repaired isogenic organoids, this was insufficient to fully rescue the AIPL1 loss-of-function disease phenotype.
Article

Ebola virus infection induces a delayed type I IFN response in bystander cells and the shutdown of key liver genes in human iPSC-derived hepatocytes

  • Whitney A. Scoon,
  • Liliana Mancio-Silva,
  • Ellen L. Suder,
  • Carlos Villacorta-Martin,
  • Jonathan Lindstrom-Vautrin,
  • John G. Bernbaum,
  • Steve Mazur,
  • Reed F. Johnson,
  • Judith Olejnik,
  • Elizabeth Y. Flores,
  • Aditya Mithal,
  • Feiya Wang,
  • Adam J. Hume,
  • Joseph E. Kaserman,
  • Sandra March-Riera,
  • Andrew A. Wilson,
  • Sangeeta N. Bhatia,
  • Elke Mühlberger,
  • Gustavo Mostoslavsky
First published:September 08, 2022
Here, Scoon and colleagues present an iPSC-based model for investigating Ebola virus infection of human primary-like hepatocytes. EBOV infection led to a general downregulation of liver function genes and a delayed interferon response in non-infected bystander cells with no inflammatory signature. This model can be used to further explore host response dynamics in a critical cell type of EBOV pathogenesis.
Article

Frizzled-6 promotes hematopoietic stem/progenitor cell mobilization and survival during LPS-induced emergency myelopoiesis

  • Trieu Hai Nguyen,
  • Belma Melda Abidin,
  • Krista M. Heinonen
First published:September 08, 2022
WNT signaling plays important roles in HSPC maintenance and expansion. In this article, Heinonen and colleagues show that the WNT/polarity pathway receptor FZD6 enhances HSPC mobilization, suppresses inflammation, and protects HSPCs from inflammation-induced cell death during emergency granulopoiesis. FZD6 could thus be targeted to promote HSPC survival and expansion under myelotoxic stress or after hematopoietic cell transplantation.
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