The role of Lin28b in myeloid and mast cell differentiation and mast cell malignancy

L. D. Wang, T. N. Rao, R. G. Rowe, P. T. Nguyen, J. L. Sullivan, D. S. Pearson, S. Doulatov, L. Wu, R. C. Lindsley, H. Zhu, D. J. Deangelo, G. Q. Daley, A. J. Wagers

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Mast cells (MCs) are critical components of the innate immune system and important for host defense, allergy, autoimmunity, tissue regeneration and tumor progression. Dysregulated MC development leads to systemic mastocytosis (SM), a clinically variable but often devastating family of hematologic disorders. Here we report that induced expression of Lin28, a heterochronic gene and pluripotency factor implicated in driving a fetal hematopoietic program, caused MC accumulation in adult mice in target organs such as the skin and peritoneal cavity. In vitro assays revealed a skewing of myeloid commitment in LIN28B-expressing hematopoietic progenitors, with increased levels of LIN28B in common myeloid and basophil-MC progenitors altering gene expression patterns to favor cell fate choices that enhanced MC specification. In addition, LIN28B-induced MCs appeared phenotypically and functionally immature, and in vitro assays suggested a slowing of MC terminal differentiation in the context of LIN28B upregulation. Finally, interrogation of human MC leukemia samples revealed upregulation of LIN28B in abnormal MCs from patients with SM. This work identifies Lin28 as a novel regulator of innate immune function and a new protein of interest in MC disease.

Original languageEnglish (US)
Pages (from-to)1320-1330
Number of pages11
JournalLeukemia
Volume29
Issue number6
DOIs
StatePublished - Jun 9 2015

Fingerprint

Myeloid Cells
Mast Cells
Cell Differentiation
Neoplasms
Systemic Mastocytosis
Mast-Cell Leukemia
Up-Regulation
Mastocytosis
Basophils
Peritoneal Cavity
Cellular Structures
Autoimmunity
Regeneration
Immune System
Hypersensitivity
Gene Expression
Skin
Genes

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Wang, L. D., Rao, T. N., Rowe, R. G., Nguyen, P. T., Sullivan, J. L., Pearson, D. S., ... Wagers, A. J. (2015). The role of Lin28b in myeloid and mast cell differentiation and mast cell malignancy. Leukemia, 29(6), 1320-1330. https://doi.org/10.1038/leu.2015.19

The role of Lin28b in myeloid and mast cell differentiation and mast cell malignancy. / Wang, L. D.; Rao, T. N.; Rowe, R. G.; Nguyen, P. T.; Sullivan, J. L.; Pearson, D. S.; Doulatov, S.; Wu, L.; Lindsley, R. C.; Zhu, H.; Deangelo, D. J.; Daley, G. Q.; Wagers, A. J.

In: Leukemia, Vol. 29, No. 6, 09.06.2015, p. 1320-1330.

Research output: Contribution to journalArticle

Wang, LD, Rao, TN, Rowe, RG, Nguyen, PT, Sullivan, JL, Pearson, DS, Doulatov, S, Wu, L, Lindsley, RC, Zhu, H, Deangelo, DJ, Daley, GQ & Wagers, AJ 2015, 'The role of Lin28b in myeloid and mast cell differentiation and mast cell malignancy', Leukemia, vol. 29, no. 6, pp. 1320-1330. https://doi.org/10.1038/leu.2015.19
Wang LD, Rao TN, Rowe RG, Nguyen PT, Sullivan JL, Pearson DS et al. The role of Lin28b in myeloid and mast cell differentiation and mast cell malignancy. Leukemia. 2015 Jun 9;29(6):1320-1330. https://doi.org/10.1038/leu.2015.19
Wang, L. D. ; Rao, T. N. ; Rowe, R. G. ; Nguyen, P. T. ; Sullivan, J. L. ; Pearson, D. S. ; Doulatov, S. ; Wu, L. ; Lindsley, R. C. ; Zhu, H. ; Deangelo, D. J. ; Daley, G. Q. ; Wagers, A. J. / The role of Lin28b in myeloid and mast cell differentiation and mast cell malignancy. In: Leukemia. 2015 ; Vol. 29, No. 6. pp. 1320-1330.
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