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Measuring single-cell density with high throughput enables dynamic profiling of immune cell and drug response from patient samples.
Wu, Weida; Ishamuddin, Sarah H; Quinn, Thomas W; Yerrum, Smitha; Zhang, Ye; Debaize, Lydie L; Kao, Pei-Lun; Duquette, Sarah Marie; Murakami, Mark A; Mohseni, Morvarid; Chow, Kin-Hoe; Miettinen, Teemu P; Ligon, Keith L; Manalis, Scott R.
Afiliação
  • Wu W; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main St building 76, Cambridge, MA 02139, USA.
  • Ishamuddin SH; Department of Biological Engineering, Massachusetts Institute of Technology, 21 Ames St #56-651, Cambridge, MA 02139, USA.
  • Quinn TW; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main St building 76, Cambridge, MA 02139, USA.
  • Yerrum S; Center for Patient-Derived Models, Dana-Farber Cancer Institute, 21 Burlington Ave, Boston, MA 02215, USA.
  • Zhang Y; Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA.
  • Debaize LL; Center for Patient-Derived Models, Dana-Farber Cancer Institute, 21 Burlington Ave, Boston, MA 02215, USA.
  • Kao PL; Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA.
  • Duquette SM; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main St building 76, Cambridge, MA 02139, USA.
  • Murakami MA; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
  • Mohseni M; Center for Patient-Derived Models, Dana-Farber Cancer Institute, 21 Burlington Ave, Boston, MA 02215, USA.
  • Chow KH; Department of Pathology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA.
  • Miettinen TP; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main St building 76, Cambridge, MA 02139, USA.
  • Ligon KL; Department of Biological Engineering, Massachusetts Institute of Technology, 21 Ames St #56-651, Cambridge, MA 02139, USA.
  • Manalis SR; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
bioRxiv ; 2024 Apr 28.
Article em En | MEDLINE | ID: mdl-38712225
ABSTRACT
Cell density, the ratio of cell mass to volume, is an indicator of molecular crowding and therefore a fundamental determinant of cell state and function. However, existing density measurements lack the precision or throughput to quantify subtle differences in cell states, particularly in primary samples. Here we present an approach for measuring the density of 30,000 single cells per hour with a precision of 0.03% (0.0003 g/mL) by integrating fluorescence exclusion microscopy with a suspended microchannel resonator. Applying this approach to human lymphocytes, we discovered that cell density and its variation decrease as cells transition from quiescence to a proliferative state, suggesting that the level of molecular crowding decreases and becomes more regulated upon entry into the cell cycle. Using a pancreatic cancer patient-derived xenograft model, we found that the ex vivo density response of primary tumor cells to drug treatment can predict in vivo tumor growth response. Our method reveals unexpected behavior in molecular crowding during cell state transitions and suggests density as a new biomarker for functional precision medicine.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: BioRxiv Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: BioRxiv Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos