Pluripotent Stem Cells Overview

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Questions and Answers

What are the two main characteristics of stem cells?

Ability to differentiate into different cell types and unspecialized cells capable of renewal (correct)

Exposure to specific growth factors and ability to form embryoid bodies

Formation of teratomas and ability to integrate into host cells

Ability to clone other cells and undergo apoptosis

Which term best describes stem cells that can differentiate into cell types derived from all three embryonic germ layers?

Totipotent

Unipotent

Multipotent

Pluripotent (correct)

Which of the following is NOT a type of pluripotent stem cell?

Multipotent stem cells (correct)

Induced pluripotent stem cells

Embryonic stem cells

Embryonic carcinoma cells

What is one criterion for maintaining pluripotency in embryonic stem cells?

Promotion of proliferation Signup and view all the answers

What role does Nanog play in stem cell pluripotency?

It activates downstream effectors of LIF and BMP signals Signup and view all the answers

What is a common demonstration of pluripotency in vivo?

Teratoma formation in nude mice Signup and view all the answers

Which of the following factors is essential in maintaining embryonic stem cell pluripotency?

LIF Signup and view all the answers

How does Sox2 function in embryonic stem cells?

It prevents differentiation and is essential for embryonal development Signup and view all the answers

What signifies the immortality of pluripotent stem cells?

Their capability of self-renewal Signup and view all the answers

What is a feature of embryonic carcinoma cells?

They are derived from teratomas Signup and view all the answers

Which transcription factors are involved in the regulation of mouse embryonic stem cell proliferation?

Oct4 and Nanog Signup and view all the answers

What role does Zic3 play in pluripotency regulation?

Maintains expression of Nanog Signup and view all the answers

What changes occur in the cell nucleus during differentiation of ES cells?

Nucleus shrinks and changes in heterochromatin distribution occur Signup and view all the answers

Which histone marks are associated with bivalent domains in the pluripotent epigenome?

H3K4me and H3K9me Signup and view all the answers

Which of the following best describes the chromatin status in pluripotent ES cells?

Euchromatin mainly exists with some heterochromatin Signup and view all the answers

Which factors activate the cell cycle progression in mouse embryonic stem cells?

b-Myb and Nanog Signup and view all the answers

Which of the following is NOT a marker for endoderm lineage specification?

Nanog Signup and view all the answers

What characterizes the hyperdynamic nature of chromatin proteins in embryonic stem cells?

Contributes to the maintenance of euchromatin Signup and view all the answers

Which signaling pathway is primarily stimulated by Eras and Tcl1 to promote the cell cycle in mouse ES cells?

PI3K/Akt signaling pathway Signup and view all the answers

What is the direct role of Sox2 in mouse embryonic stem cells?

Maintains pluripotency alongside Oct4 and Nanog Signup and view all the answers

What is the primary function of Leukaemia inhibitory factor (LIF) in maintaining pluripotency?

Acts as a receptor in the Jak/Stat signaling pathway Signup and view all the answers

How does c-Myc contribute to stem cell signaling?

It serves as a downstream effector of STAT3 Signup and view all the answers

What happens to embryonic stem cells (ES cells) when LIF is absent?

They undergo spontaneous differentiation into primitive endoderm-like cells Signup and view all the answers

Which transcription factor is known for its dual role as an oncogene and tumor suppressor?

Klf4 Signup and view all the answers

What is the result of c-Myc's interaction with GSK3b in the Wnt signaling pathway?

Compensates for the anti-proliferative effects of Klf4 Signup and view all the answers

Which component is essential for the activation of Stat3 in teratogenic differentiation processes?

LIF receptor Signup and view all the answers

What is the main role of pluripotent cells in the mouse embryo?

They contribute to the formation of the ICM of the blastocyst Signup and view all the answers

What overall effect does the overexpression of Klf4 have on embryonic stem cells?

Inhibits differentiation of ES cells Signup and view all the answers

Which process is indicated by removing Oct3/4 and adding Cdx2 to ES cell culture?

Facilitating differentiation into trophectoderm-like cells Signup and view all the answers

What factor is necessary for the maintenance of mouse embryonic stem cell pluripotency in vitro?

The presence of serum and LIF Signup and view all the answers

Study Notes

Pluripotency Stem Cells

Pluripotent stem cells are master cells with two important characteristics:
- Unspecialized cells capable of self-renewal
- Ability to differentiate into various cell types
These cells have different differentiation potentials, including:
- Totipotent
- Pluripotent
- Multipotent
- Unipotent

Pluripotent Stem Cells - Characteristics

Derived from the Latin word "plures," meaning "several" or "many."
Typically used to describe stem cells that generate cells from all three embryonic germ layers.

Pluripotent Stem Cell Types

Embryonic stem cells
Embryonic carcinoma cells
Embryonic germ cells
Induced pluripotent stem cells

Origins of Pluripotent Cells

Embryonic carcinoma cells form teratomas.
Abnormal karyotypes are common in embryonic carcinoma cells.
Germline transmission is rare in these cells.
Pluripotent cells originate from the inner cell mass (ICM) of a blastocyst.

Criteria for Pluripotency

Immortality
Undifferentiation
Clonality
Broad developmental potential

In Vitro Demonstration of Pluripotency

Differentiation triggered when grown in suspension, forming embryoid bodies.
Different cell types are spontaneously obtained.
Specific growth factors direct ES cell differentiation.

In Vivo Demonstration of Pluripotency

Teratoma formation when injected into a nude mouse.
ES cells integrate, proliferate, and differentiate into germ lineages (including germ cells) when injected into a host blastocyst.

Regulation of Pluripotency in ES Cells

Pluripotency is maintained by promoting proliferation and inhibiting differentiation.

Epigenetic Modifications and Pluripotency

Epigenetic modifications regulate pluripotency.
Transcription factors are involved in ES cell pluripotency.

Factors Required for Pluripotency

Nanog
Oct 3/4
Sox 2
LIF
c-Myc
Klf4
Zic3

Core Regulatory Circuitry in ES Cells

Core factors (Nanog, Sox2, Oct4) activate expression of target genes.
Signaling components regulate pluripotency/self-renewal.
Differentiation-promoting genes are regulated.

Nanog

A transcription factor containing a homeobox domain.
Downstream effects of signals from LIF and BMP.
Elevated levels exclude LIF and feeder layer inclusion.
Works with other key factors, including Oct4 and Sox2.

Oct 3/4

A POU-domain transcription factor.
Maintains pluripotency in ES, EGCs, and ECCs.
Tightly regulated, associated with target genes for maintenance.
Regulatory elements in target genes are close to Sox2 binding sites.
Key factor in self-renewing stem cell framework.

Sox2

Member of the HMG-domain DNA-binding family.
Critical for embryonic development and preventing ES cell differentiation.
Many ES cell pluripotency-associated genes are co-regulated by Sox2 and Oct3/4.
Forms a ternary complex with Oct4/Oct1 and Fgf4 for function.
Cooperates with other TFs (e.g., Nanog) to activate pluripotency markers.

LIF

Interleukin-6 cytokine family member.
Essential for maintaining pluripotency in vitro.
Binds to a heterodimeric receptor (LIFR and gp130).
Binding activates the JAK/STAT signal transduction pathway.
Activated Stat3 maintains pluripotency.

Combinatorial Signaling Pathways

LIF and master regulator genes are involved in maintaining mouse ESC pluripotency.

c-Myc

Helix-loop-helix/leucine zipper transcription factor.
Cellular function.
Downstream effector of STAT3 in LIF receptor signaling pathway.
A substrate for GSK3b in Wnt signaling pathway.
Compensates for anti-proliferative effects of Klf4, especially in iPS cells.

Klf4

Member of a quartet having a Kruppel-type zinc finger transcription factor.
Can act as an oncogene and a tumor suppressor protein.
Overexpression inhibits ES cell differentiation.
Upregulates with Oct3/4.
Role potentially limited to specific target genes.
Represses p53, a negative regulator of Nanog.

Pluripotent Lineages in the Mouse Embryo

Stages in mouse embryo development, showing lineages like germ cell, stem cell, etc.

Pluripotent Cell Formation in Mouse Blastocysts

ICM forms pluripotent cells.
Primitive endoderm forms on ICM's surface.
Pluripotent cells become epiblast and proliferate.
Form primitive ectoderm.
Lineage restriction occurs.
Lineage commitment to germ and somatic cells.

Differentiation of Mouse ES Cells

Differentiates into three cell types (primitive endoderm, trophectoderm, primitive ectoderm).
Mimics pluripotent stem cell differentiation in early embryos.
LIF absence and Oct3/4 abundance promotes primitive endoderm cells.
Nanog absence and Gata6 presence promotes parietal endoderm cells.
Oct3/4 removal and Cdx2 addition encourages trophectoderm formation.

Regulation of Mouse ES Cell Proliferation

Pluripotent transcription factors activate effectors for ES cell proliferation.
Eras and Tcl1 stimulate PI3K/Akt signaling for cell cycle advancement.
Other factors (b-Myb and c-Myc) directly promote cell cycle progression.

Transcriptional Regulation of Oct3/4

Various factors (e.g., Sox2, Cdx2, Lrh1) regulate Oct3/4 expression.

Zic3

Contributes to pluripotency maintenance by operating downstream from Oct4, Nanog, and Sox2.
Inhibits endoderm lineage determination.
The presence of Zic3 maintains homeodomain protein Nanog expression.

Epigenetic Regulations of ES Cells Pluripotency

Changes in the nucleus and distribution of chromatan occur.
Epigenetic changes accompany ES cell differentiation.

Characteristics of the Pluripotent Epigenome

Nucleus shrinks; chromatan distribution shifts.

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Description

This quiz explores the characteristics and types of pluripotent stem cells, including their origins and differentiation potentials. It covers key terminology and essential concepts related to these master cells, suitable for students studying cell biology or regenerative medicine.