Dissecting engineered cell types and enhancing cell fate conversion via CellNet

Samantha A. Morris, Patrick Cahan, Hu Li, Anna M. Zhao, Adrianna K. San Roman, Ramesh A. Shivdasani, James J. Collins, George Q. Daley

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Engineering clinically relevant cells in vitro holds promise for regenerative medicine, but most protocols fail to faithfully recapitulate target cell properties. To address this, we developed CellNet, a network biology platform that determines whether engineered cells are equivalent to their target tissues, diagnoses aberrant gene regulatory networks, and prioritizes candidate transcriptional regulators to enhance engineered conversions. Using CellNet, we improved B cell to macrophage conversion, transcriptionally and functionally, by knocking down predicted B cell regulators. Analyzing conversion of fibroblasts to induced hepatocytes (iHeps), CellNet revealed an unexpected intestinal program regulated by the master regulator Cdx2. We observed long-term functional engraftment of mouse colon by iHeps, thereby establishing their broader potential as endoderm progenitors and demonstrating direct conversion of fibroblasts into intestinal epithelium. Our studies illustrate how CellNet can be employed to improve direct conversion and to uncover unappreciated properties of engineered cells.

Original languageEnglish (US)
Pages (from-to)889-902
Number of pages14
JournalCell
Volume158
Issue number4
DOIs
StatePublished - Aug 14 2014

Fingerprint

Fibroblasts
Cells
Macrophages
Hepatocytes
B-Lymphocytes
Genes
Tissue
Choristoma
Endoderm
Regenerative Medicine
Gene Regulatory Networks
Intestinal Mucosa
Colon

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Morris, S. A., Cahan, P., Li, H., Zhao, A. M., San Roman, A. K., Shivdasani, R. A., ... Daley, G. Q. (2014). Dissecting engineered cell types and enhancing cell fate conversion via CellNet. Cell, 158(4), 889-902. https://doi.org/10.1016/j.cell.2014.07.021

Dissecting engineered cell types and enhancing cell fate conversion via CellNet. / Morris, Samantha A.; Cahan, Patrick; Li, Hu; Zhao, Anna M.; San Roman, Adrianna K.; Shivdasani, Ramesh A.; Collins, James J.; Daley, George Q.

In: Cell, Vol. 158, No. 4, 14.08.2014, p. 889-902.

Research output: Contribution to journalArticle

Morris, SA, Cahan, P, Li, H, Zhao, AM, San Roman, AK, Shivdasani, RA, Collins, JJ & Daley, GQ 2014, 'Dissecting engineered cell types and enhancing cell fate conversion via CellNet', Cell, vol. 158, no. 4, pp. 889-902. https://doi.org/10.1016/j.cell.2014.07.021
Morris SA, Cahan P, Li H, Zhao AM, San Roman AK, Shivdasani RA et al. Dissecting engineered cell types and enhancing cell fate conversion via CellNet. Cell. 2014 Aug 14;158(4):889-902. https://doi.org/10.1016/j.cell.2014.07.021
Morris, Samantha A. ; Cahan, Patrick ; Li, Hu ; Zhao, Anna M. ; San Roman, Adrianna K. ; Shivdasani, Ramesh A. ; Collins, James J. ; Daley, George Q. / Dissecting engineered cell types and enhancing cell fate conversion via CellNet. In: Cell. 2014 ; Vol. 158, No. 4. pp. 889-902.
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