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Using mouse models to study function of transcriptional factors in T cell development.

Li P, Xiao Y, Liu Z, Liu P - Cell Regen (Lond) (2012)

Bottom Line: With the advances of genetic engineering and conditional knockout (CKO) mice, we now understand hematopoiesis is a dynamic stepwise process starting from hematopoietic stem cells (HSCs) which are responsible for replenishing all blood cells.Transcriptional factors play important role in hematopoiesis.Finally, we focused on the key transcriptional factor Bcl11b and its function in regulating T cell specification and commitment.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Regenerative Biology, Guangzchou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China ; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou, China.

ABSTRACT
Laboratory mice have widely been used as tools for basic biological research and models for studying human diseases. With the advances of genetic engineering and conditional knockout (CKO) mice, we now understand hematopoiesis is a dynamic stepwise process starting from hematopoietic stem cells (HSCs) which are responsible for replenishing all blood cells. Transcriptional factors play important role in hematopoiesis. In this review we compile several studies on using genetic modified mice and humanized mice to study function of transcriptional factors in lymphopoiesis, including T lymphocyte and Natural killer (NK) cell development. Finally, we focused on the key transcriptional factor Bcl11b and its function in regulating T cell specification and commitment.

No MeSH data available.


Related in: MedlinePlus

Summary of reprogram from various T cell subsets to ITNK cells. ETP, early T cell precursors; DN, double negative; DP, double positive; SP, single positive; ITNK, Induced T to natural killer cells; NKP, natural killer progenitors; NK, natural killer cells. Black arrows indicate differentiation and red arrows indicate reprogramming.
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Fig5: Summary of reprogram from various T cell subsets to ITNK cells. ETP, early T cell precursors; DN, double negative; DP, double positive; SP, single positive; ITNK, Induced T to natural killer cells; NKP, natural killer progenitors; NK, natural killer cells. Black arrows indicate differentiation and red arrows indicate reprogramming.

Mentions: Using Bcl11b conditional knockout mice, it was demonstrated that Bcl11b is important for both early and mature T cell development. Positively regulated by Notch signaling, Bcl11b suppresses key NK genes expression and promotes the expression of cocktail of T cell-associated transcription factors in T cells. Thus, acute loss of Bcl11b makes early T cells lose their T cell potential and differentiate to NK cells. In committed DN3 thymocytes, Bcl11b is essential for the maintenance of T cell identity, since every single survival Bcl11b deficient DN3 T cell abandons its T cell development program and subsequently reprograms to ITNK. Similarly, mature T cells transdifferentiate to ITNK upon loss of Bcl11b. In a word, Bcl11b is indispensable for T cells at all developmental stages to sustain T cell development and maintain T cell identity, while suppress NK cell program (Figure‚ÄČ5) [6].Figure 5


Using mouse models to study function of transcriptional factors in T cell development.

Li P, Xiao Y, Liu Z, Liu P - Cell Regen (Lond) (2012)

Summary of reprogram from various T cell subsets to ITNK cells. ETP, early T cell precursors; DN, double negative; DP, double positive; SP, single positive; ITNK, Induced T to natural killer cells; NKP, natural killer progenitors; NK, natural killer cells. Black arrows indicate differentiation and red arrows indicate reprogramming.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230505&req=5

Fig5: Summary of reprogram from various T cell subsets to ITNK cells. ETP, early T cell precursors; DN, double negative; DP, double positive; SP, single positive; ITNK, Induced T to natural killer cells; NKP, natural killer progenitors; NK, natural killer cells. Black arrows indicate differentiation and red arrows indicate reprogramming.
Mentions: Using Bcl11b conditional knockout mice, it was demonstrated that Bcl11b is important for both early and mature T cell development. Positively regulated by Notch signaling, Bcl11b suppresses key NK genes expression and promotes the expression of cocktail of T cell-associated transcription factors in T cells. Thus, acute loss of Bcl11b makes early T cells lose their T cell potential and differentiate to NK cells. In committed DN3 thymocytes, Bcl11b is essential for the maintenance of T cell identity, since every single survival Bcl11b deficient DN3 T cell abandons its T cell development program and subsequently reprograms to ITNK. Similarly, mature T cells transdifferentiate to ITNK upon loss of Bcl11b. In a word, Bcl11b is indispensable for T cells at all developmental stages to sustain T cell development and maintain T cell identity, while suppress NK cell program (Figure‚ÄČ5) [6].Figure 5

Bottom Line: With the advances of genetic engineering and conditional knockout (CKO) mice, we now understand hematopoiesis is a dynamic stepwise process starting from hematopoietic stem cells (HSCs) which are responsible for replenishing all blood cells.Transcriptional factors play important role in hematopoiesis.Finally, we focused on the key transcriptional factor Bcl11b and its function in regulating T cell specification and commitment.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Regenerative Biology, Guangzchou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China ; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou, China.

ABSTRACT
Laboratory mice have widely been used as tools for basic biological research and models for studying human diseases. With the advances of genetic engineering and conditional knockout (CKO) mice, we now understand hematopoiesis is a dynamic stepwise process starting from hematopoietic stem cells (HSCs) which are responsible for replenishing all blood cells. Transcriptional factors play important role in hematopoiesis. In this review we compile several studies on using genetic modified mice and humanized mice to study function of transcriptional factors in lymphopoiesis, including T lymphocyte and Natural killer (NK) cell development. Finally, we focused on the key transcriptional factor Bcl11b and its function in regulating T cell specification and commitment.

No MeSH data available.


Related in: MedlinePlus