C‐Myc‐induced survivin is essential for promoting the Notch-dependent t cell differentiation from hematopoietic stem cells

Rizwanul Haque, Jianyong Song, Mohammad Haque, Fengyang Lei, Praneet Sandhu, Bing Ni, Songguo Zheng, Deyu Fang, Jin Ming Yang, Jianxun Song

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Notch is indispensable for T cell lineage commitment, and is needed for thymocyte differentiation at early phases. During early stages of T cell development, active Notch prevents other lineage potentials including B cell lineage and myeloid cell (e.g., dendritic cell) lineage. Nevertheless, the precise intracellular signaling pathways by which Notch promotes T cell differentiation remain unclear. Here we report that the transcription factor c‐Myc is a key mediator of the Notch signaling–regulated T cell differentiation. In a well‐established in vitro differentiation model of T lymphocytes from hematopoietic stem cells, we showed that Notch1 and 4 directly promoted c‐Myc expression; dominant‐negative (DN) c‐Myc inhibited early T cell differentiation. Moreover, the c‐Myc expression activated by Notch signaling increased the expression of survivin, an inhibitor of apoptosis (IAP) protein. We further demonstrated that over‐expression of c‐Myc increased the abundance of survivin and the T cell differentiation thereof, whereas dn c‐Myc reduced survivin levels and concomitantly retarded the differentiation. The c‐Myc–dependent survivin induction is functionally germane, because Notch‐dependent T cell differentiation was canceled by the depletion of survivin. These results identify both c‐Myc and survivin as important mediators of the Notch signaling–regulated differentiation of T lymphocytes from hematopoietic stem cells.

Original languageEnglish (US)
Article number97
JournalGenes
Volume8
Issue number3
DOIs
StatePublished - Mar 2017

Fingerprint

Hematopoietic Stem Cells
Cell Differentiation
T-Lymphocytes
Cell Lineage
Inhibitor of Apoptosis Proteins
Myeloid Cells
Thymocytes
Dendritic Cells
B-Lymphocytes
Transcription Factors

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Haque, Rizwanul ; Song, Jianyong ; Haque, Mohammad ; Lei, Fengyang ; Sandhu, Praneet ; Ni, Bing ; Zheng, Songguo ; Fang, Deyu ; Yang, Jin Ming ; Song, Jianxun. / C‐Myc‐induced survivin is essential for promoting the Notch-dependent t cell differentiation from hematopoietic stem cells. In: Genes. 2017 ; Vol. 8, No. 3.
@article{99af4e2a41cc448fbf9cbcd36e96ac8d,
title = "C‐Myc‐induced survivin is essential for promoting the Notch-dependent t cell differentiation from hematopoietic stem cells",
abstract = "Notch is indispensable for T cell lineage commitment, and is needed for thymocyte differentiation at early phases. During early stages of T cell development, active Notch prevents other lineage potentials including B cell lineage and myeloid cell (e.g., dendritic cell) lineage. Nevertheless, the precise intracellular signaling pathways by which Notch promotes T cell differentiation remain unclear. Here we report that the transcription factor c‐Myc is a key mediator of the Notch signaling–regulated T cell differentiation. In a well‐established in vitro differentiation model of T lymphocytes from hematopoietic stem cells, we showed that Notch1 and 4 directly promoted c‐Myc expression; dominant‐negative (DN) c‐Myc inhibited early T cell differentiation. Moreover, the c‐Myc expression activated by Notch signaling increased the expression of survivin, an inhibitor of apoptosis (IAP) protein. We further demonstrated that over‐expression of c‐Myc increased the abundance of survivin and the T cell differentiation thereof, whereas dn c‐Myc reduced survivin levels and concomitantly retarded the differentiation. The c‐Myc–dependent survivin induction is functionally germane, because Notch‐dependent T cell differentiation was canceled by the depletion of survivin. These results identify both c‐Myc and survivin as important mediators of the Notch signaling–regulated differentiation of T lymphocytes from hematopoietic stem cells.",
author = "Rizwanul Haque and Jianyong Song and Mohammad Haque and Fengyang Lei and Praneet Sandhu and Bing Ni and Songguo Zheng and Deyu Fang and Yang, {Jin Ming} and Jianxun Song",
year = "2017",
month = "3",
doi = "10.3390/genes8030097",
language = "English (US)",
volume = "8",
journal = "Genes",
issn = "2073-4425",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "3",

}

Haque, R, Song, J, Haque, M, Lei, F, Sandhu, P, Ni, B, Zheng, S, Fang, D, Yang, JM & Song, J 2017, 'C‐Myc‐induced survivin is essential for promoting the Notch-dependent t cell differentiation from hematopoietic stem cells', Genes, vol. 8, no. 3, 97. https://doi.org/10.3390/genes8030097

C‐Myc‐induced survivin is essential for promoting the Notch-dependent t cell differentiation from hematopoietic stem cells. / Haque, Rizwanul; Song, Jianyong; Haque, Mohammad; Lei, Fengyang; Sandhu, Praneet; Ni, Bing; Zheng, Songguo; Fang, Deyu; Yang, Jin Ming; Song, Jianxun.

In: Genes, Vol. 8, No. 3, 97, 03.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - C‐Myc‐induced survivin is essential for promoting the Notch-dependent t cell differentiation from hematopoietic stem cells

AU - Haque, Rizwanul

AU - Song, Jianyong

AU - Haque, Mohammad

AU - Lei, Fengyang

AU - Sandhu, Praneet

AU - Ni, Bing

AU - Zheng, Songguo

AU - Fang, Deyu

AU - Yang, Jin Ming

AU - Song, Jianxun

PY - 2017/3

Y1 - 2017/3

N2 - Notch is indispensable for T cell lineage commitment, and is needed for thymocyte differentiation at early phases. During early stages of T cell development, active Notch prevents other lineage potentials including B cell lineage and myeloid cell (e.g., dendritic cell) lineage. Nevertheless, the precise intracellular signaling pathways by which Notch promotes T cell differentiation remain unclear. Here we report that the transcription factor c‐Myc is a key mediator of the Notch signaling–regulated T cell differentiation. In a well‐established in vitro differentiation model of T lymphocytes from hematopoietic stem cells, we showed that Notch1 and 4 directly promoted c‐Myc expression; dominant‐negative (DN) c‐Myc inhibited early T cell differentiation. Moreover, the c‐Myc expression activated by Notch signaling increased the expression of survivin, an inhibitor of apoptosis (IAP) protein. We further demonstrated that over‐expression of c‐Myc increased the abundance of survivin and the T cell differentiation thereof, whereas dn c‐Myc reduced survivin levels and concomitantly retarded the differentiation. The c‐Myc–dependent survivin induction is functionally germane, because Notch‐dependent T cell differentiation was canceled by the depletion of survivin. These results identify both c‐Myc and survivin as important mediators of the Notch signaling–regulated differentiation of T lymphocytes from hematopoietic stem cells.

AB - Notch is indispensable for T cell lineage commitment, and is needed for thymocyte differentiation at early phases. During early stages of T cell development, active Notch prevents other lineage potentials including B cell lineage and myeloid cell (e.g., dendritic cell) lineage. Nevertheless, the precise intracellular signaling pathways by which Notch promotes T cell differentiation remain unclear. Here we report that the transcription factor c‐Myc is a key mediator of the Notch signaling–regulated T cell differentiation. In a well‐established in vitro differentiation model of T lymphocytes from hematopoietic stem cells, we showed that Notch1 and 4 directly promoted c‐Myc expression; dominant‐negative (DN) c‐Myc inhibited early T cell differentiation. Moreover, the c‐Myc expression activated by Notch signaling increased the expression of survivin, an inhibitor of apoptosis (IAP) protein. We further demonstrated that over‐expression of c‐Myc increased the abundance of survivin and the T cell differentiation thereof, whereas dn c‐Myc reduced survivin levels and concomitantly retarded the differentiation. The c‐Myc–dependent survivin induction is functionally germane, because Notch‐dependent T cell differentiation was canceled by the depletion of survivin. These results identify both c‐Myc and survivin as important mediators of the Notch signaling–regulated differentiation of T lymphocytes from hematopoietic stem cells.

UR - http://www.scopus.com/inward/record.url?scp=85014609226&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85014609226&partnerID=8YFLogxK

U2 - 10.3390/genes8030097

DO - 10.3390/genes8030097

M3 - Article

C2 - 28272325

AN - SCOPUS:85014609226

VL - 8

JO - Genes

JF - Genes

SN - 2073-4425

IS - 3

M1 - 97

ER -